Second-year running back Isaac Guerendo opens the season third on the 49ers' depth chart, though he may already see more action than originally anticipated. Christian McCaffrey (calf) popped up on the team's injury report this week and is tagged as questionable for San Francisco's Week 1 matchup against the Seahawks. Guerendo's only route to fantasy relevance relies on CMC sitting. If that does happen, then he can be seen as a deep-league flex candidate. Brian Robinson Jr. will likely draw the start, but Guerendo made his mark in 2024 in similar circumstances and is a potential RB4/5 pending McCaffrey's status.

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Rookie running back Jordan James (finger) is listed as doubtful for the 49ers' season opener against the Seattle Seahawks after being a limited participant in practice all week. The fifth-rounder out of Oregon suffered a broken finger in early August, which precluded him from playing at all in the preseason. Early in camp, James was thought to be a valid challenger to Isaac Guerendo to back up Christian McCaffrey (calf), a competition rendered moot with the acquisition of Brian Robinson Jr.. Even with McCaffrey listed as questionable for Week 1, an injured James has no place on fantasy rosters.

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Brian Robinson Jr.'s fantasy stock took a hit when he was sent from the Commanders to the 49ers in August, going from presumed starter to second-stringer overnight. However, with Christian McCaffrey (calf) landing on the team's injury report just days before San Francisco's season opener, Robinson may already be in the spotlight again. McCaffrey is questionable for Week 1 after following a limited practice on Thursday with a DNP on Friday. Should CMC sit, Robinson will be first in line for the start, and thus viable for fantasy purposes. Even if that is the case, it is hard to envision anything higher than a borderline RB2/3 finish for Robinson as he is still learning the system and would likely be splitting work with second-year back Isaac Guerendo.

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Brock Purdy opens the 2025 season against the Seattle Seahawks on Sunday. In two starts against his division rival last season, Purdy was 39-for-56 (70% completion rate) for 414 yards, four touchdowns, and one interception. In five career starts against Seattle, Purdy has nine touchdowns to three interceptions and has averaged 241.6 passing yards per game. With running back Christian McCaffrey (calf) drawing a questionable tag for the season opener, there may be increased reliance on Purdy's arm. Fortunately, wide receiver Jauan Jennings (calf) has been cleared for the game and will join George Kittle and Ricky Pearsall as Purdy's top targets downfield. Fantasy football managers can start Purdy as he still has enough support around him to finish as a low-end QB1.

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New York Giants kicker Graham Gano is a difficult fantasy start for Week 1, given his recent injury history and the unknown offensive output of the team. Gano has missed significant time over the last two seasons due to injury and saw his field goal percentage drop to 73.25% over the past two seasons. While he did show a positive sign by making both of his 50+ yard attempts, his overall inconsistency is a major concern. The Giants' offense is expected to be a work in progress with a new quarterback, which could limit scoring opportunities. While the Commanders' defense wasn't particularly stingy against kickers last year, Gano's recent struggles make him a high-risk, low-reward option to start the season.

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Washington Commanders running back Jeremy McNichols is back for his second season with the team after earning a spot on the final roster. McNichols was a valuable player in pass protection and special teams last season, in addition to showing versatility as a runner and receiver when needed. He averaged 4.7 yards per carry and scored five touchdowns, including two in Week 4 against Arizona last season and one against Detroit in the playoffs. The 29-year-old has bounced around multiple teams before Washington, but has carved out a nice role on special teams and as a stout pass protector, where the coaches rave about him. McNichols won't be relevant for fantasy purposes in Week 1, but will likely be on the field for some snaps.

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New York Giants tight end Theo Johnson is a high-upside fantasy option entering his second season as the unquestioned top tight end. As a rookie in 2024, Johnson averaged 4.47 fantasy points per game and showcased his potential with 331 receiving yards. The matchup against the Washington Commanders is a difficult one, as they were the 8th-ranked fantasy defense against tight ends in 2024, allowing an average of only 9.16 points per game to the position. However, Johnson's athletic profile and newfound role as a top target for quarterback Russell Wilson make him an intriguing play with a higher ceiling than many might expect. He is a talented TE to watch out for each week.

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Washington Commanders running back Chris Rodriguez Jr. has had a strong training camp and preseason, which ultimately led to his inclusion on the final roster. Rodriguez could play a significant role as the primary early-down back in Week 1 against the Giants. He proved to be up to the task in his small sample of touches last season, leading all running backs with at least 25 rushes in Success Rate at 57%. His peripherals are all very encouraging, and then he showed up to camp after off-season training with a transformed body, looking faster and leaner. The results have been positive with him reaching 20 MPH in practice more times this year than ever before, including on a breakaway run against the Bengals in Washington's second preseason game. The backfield will be by committee, and there is a lot of uncertainty for how it will all shake out. Rodriguez is a worthwhile stash to hold through Week 1 to see what happens, but not a startable option.

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New York Giants wide receiver Darius Slayton is a long-shot fantasy option for Week 1 despite his speed and veteran presence. Coming off a season where he averaged 5.66 fantasy points per game, Slayton is not a recommended play for most fantasy leagues. The Washington Commanders' defense was the 8th-ranked fantasy defense against wide receivers in 2024, giving up 30.24 points per game. However, Slayton's role as a deep threat, combined with the presence of other receivers like Malik Nabers and Wan'Dale Robinson, will likely limit his target share. While his new quarterback, Russell Wilson, represents a potential upgrade, Slayton's fantasy value is too reliant on a big play to be trusted as a reliable starter.

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New York Giants wide receiver Wan'Dale Robinson is a risky Week 1 fantasy play despite a career-high 140 targets in 2024. He enters the season with new quarterback Russell Wilson, and he is ranked as the 57th-best fantasy wide receiver for Week 1. The matchup against the Washington Commanders does not appear favorable, as they were the 8th-ranked fantasy defense against wide receivers in 2024 by allowing an average of 30.24 points per game. Robinson's specific role as a smaller slot receiver might limit his upside. With a career-long average of just 8.2 yards per reception, his fantasy value is heavily reliant on short, high-volume passes. This makes him a risky Flex option, as his floor is dependent on receptions and his ceiling is limited by his role in the offense.

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Washington Commanders running back Austin Ekeler should handle a lot of the work in the Washington backfield in Week 1 against the Giants. Ekeler is coming off a strong bounceback season in his first year with Washington, totaling 733 yards from scrimmage with four touchdowns in 12 games. He still proved deadly as a pass catcher as he led the position in yards per reception at 10.5. Ekeler is likely to take care of the pass-down responsibilities while also maybe taking on more as a rusher this year. But he has also been aware that limiting his reps is best to keep him most effective, and they have capable backs behind him to help carry the load. Chris Rodriguez Jr. and rookie Jacory Croskey-Merritt will likely handle early-down responsibilities and earn volume in carries. Ekeler is the trusted veteran in the room and should get most of the high-value touches, receptions, and rushes inside the 10-yard line. He is a solid flex play for Week 1.

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New York Giants running back Tyrone Tracy Jr. is a promising fantasy option for his Week 1 matchup against the Washington Commanders. Coming off a solid rookie season in which he averaged 13.48 fantasy points per game, Tracy is ranked as the 22nd-best fantasy running back for the opening week. The matchup is favorable, as the Commanders' defense ranked 24th against fantasy running backs in 2024, giving up an average of 22.72 points per game. Tracy's high-volume workload, coupled with his role in the passing game, should provide a strong floor for fantasy managers. Given the porous Commanders' run defense, Tracy is a strong RB2 or FLEX play with a high ceiling.

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New York Giants rookie running back Cam Skattebo is a player to watch for later weeks, but he is not a recommended play for his Week 1 debut. The Giants drafted Skattebo in the fourth round of the 2025 NFL Draft after a standout college season with over 2,300 scrimmage yards. However, he is currently buried on the depth chart behind starting running back Tyrone Tracy Jr. and Devin Singletary. While the Commanders' defense was vulnerable to the run last season, ranking 24th against fantasy running backs and allowing 22.72 fantasy points per game, Skattebo is not expected to see enough volume to be a fantasy-relevant option in Week 1. Fantasy managers should monitor his usage, but he should remain on the bench to start the season.

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Los Angeles Chargers running back Omarion Hampton rushed for 48 yards on 15 carries during Friday's win over the Kansas City Chiefs. He also caught two passes for an additional 13 yards through the air. While it was promising that the Chargers trusted Hampton to handle heavy volume, his inefficiency (3.2 yards per carry) was somewhat worrisome. Going forward, it's possible that the rookie will need to score touchdowns in order to be fantasy relevant. Nevertheless, he is the clear No. 1 running back in Los Angeles, so his value will increase as he starts to face easier defenses. For example, he gets a much more favorable matchup in Week 2 against the Las Vegas Raiders.

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Washington Commanders rookie running back Jacory Croskey-Merritt's role in the backfield is still unclear for Week 1 against the Giants. Croskey-Merritt, or who many now refer to as "Bill," was recently listed as RB4 on the team's unofficial depth chart. It becomes a question of whether the Washington coaching staff opts to keep four running backs active on gameday. Austin Ekeler will be in line to see most of the snaps, while Chris Rodriguez Jr. and Jeremy McNichols could also be in the mix for touches and play special teams. He is the most explosive and shifty runner in Washington's running back room, which should lead to some touches even if he isn't the starter right away. Croskey-Merritt has been one of the more trendy names of draft season, and he is one of the better upside picks to take. However, the usage is tough to predict for Week 1 and should likely stay on benches.

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New York Giants quarterback Russell Wilson enters Week 1 against the Washington Commanders as a risky fantasy play. Despite a solid 2024 season with the Steelers, where he averaged 15.7 fantasy points per game, he is ranked as the 29th-best fantasy quarterback for the opening week. The Commanders' defense, which ranked 19th against fantasy quarterbacks in 2024 by allowing 15.87 points per game, presents a favorable matchup on paper. However, an injury to starting left tackle Andrew Thomas and inexperience with the other 10 starters could limit Wilson's upside. This matchup, combined with his new team and system, makes Wilson a risky play, even with a manageable defensive opponent.

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Los Angeles Chargers wide receiver Quentin Johnston converted seven targets into five catches, 79 yards, and two touchdowns during Friday's Week 1 win over the Kansas City Chiefs. The 24-year-old has struggled with drops throughout the early portion of his career, but he has still continued to flash plenty of upside, totaling 711 yards and eight touchdowns last year. After Friday's game, quarterback Justin Herbert commended Johnston and explained how easy it is for him to trust the receiver to make a play when the ball is in his hands. These comments indicate that Johnston is one of Herbert's favorite targets, vaulting him into WR3/FLEX territory for next week's contest against the Las Vegas Raiders.

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Los Angeles Chargers quarterback Justin Herbert completed 25 of his 34 pass attempts for 318 yards, three touchdowns, and zero interceptions during Friday's game against the Kansas City Chiefs. He also took three sacks and rushed for 32 yards. The former first-round pick started off the 2025 season on the right foot, and there's no indication that he's slowing down anytime soon. If anything, his schedule only gets easier in the short term as the Chargers take on the Las Vegas Raiders next week. Herbert has quickly asserted himself as a strong QB1 option in fantasy football.

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Atlanta Falcons kicker Younghoe Koo had a rough 2024, converting just 73.5 percent of his field goal attempts last season beforemissing the final three games with a hip injury. However, the 31-year-old comes into 2025 healthy and made four of five field goals in the preseason, with his only miss coming from 51 yards out. With the Falcons having an implied total of 23 in their Week 1 contest against the Buccaneers, there is expected to be a decent amountof scoring. The fact that the game is a home matchup inside the dome in Atlanta means Koo will not have to deal with the elements, providing him with a pristine kicking environment. The eighth-year pro ranks as a low-end, top 12 option for Sunday's matchup, although his upside is limited given this will only be Michael Penix Jr.'s fourth start of his career, so drives may stall quickly.

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Washington Commanders rookie wide receiver Jaylin Lane figures to serve as a depth option at receiver and handle punt return duties in Week 1 against the Giants. The trio of receivers ahead of Lane on the depth chart all finally seem to be healthy and present with the team for the first time all camp, with Noah Brown off the injury report and Terry McLaurin securing a long-term extension. Deebo Samuel Sr. has been healthy and making plays all camp, and Lane is another guy who is dynamic with the ball in his hands and can stretch the defense vertically with his 4.34 speed. The fourth-rounder started to really emerge late in training camp and in the second preseason game, showing flexibility from the slot and outside. Lane should mix into the receiver rotation and could earn a schemed touch or two on Sunday against the Giants. He is worth putting on watch lists in redraft leagues early in the season.

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