Some fantasy football managers got an early scare and a touch of PTSD on Thursday, Sept. 4, when San Francisco 49ers running back Christian McCaffrey suddenly appeared on the injury report with a calf issue.
Fans and fantasy managers will remember last year, when McCaffrey was ruled out just an hour and a half before kickoff in Week 1 against the Jets. That marked the start of an injury-plagued 2024, in which he played only four games. The new calf injury makes his 2025 outlook particularly concerning.
On Thursday, McCaffrey didn't practice as San Francisco ruled him as questionable for Sunday's matchup. That means that it could come down to the wire whether McCaffrey suits up.
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Here is who should take over for McCaffrey for the 49ers if he is unable to play due to his calf injury in Week 1 against the Seattle Seahawks.
49ers RB depth chart
| Position | Player Name |
| 1 | Christian McCaffrey |
| 2 | Brian Robinson Jr. |
| 3 | Isaac Guerendo |
Christian McCaffrey
When healthy, McCaffrey is one of the NFL’s best players. The problem is that staying healthy has become a matter of chance. He has been in the league eight years and is entering his ninth, but has played a full season in only four of those years.
The 49ers running back has appeared in 95 career games, rushing for 6,387 yards with 52 touchdowns. He has added 4,466 receiving yards and 29 receiving touchdowns. For San Francisco to have a bounce-back season, it cannot afford for McCaffrey to miss significant time, especially given the team’s ongoing injuries at wide receiver.
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Brian Robinson Jr.
Robinson Jr. was traded for a 2026 sixth-round draft pick. The 49ers didn’t give up much, but the running back is in the final year of his rookie contract. He gets a chance to audition for San Francisco during the 2025 season, as the team decides whether to keep him long-term.
Robinson’s career got off to a delayed start after he was shot in the offseason before his rookie year. He has played in 41 games over three seasons, totaling 2,329 yards and 15 touchdowns. While not known for his receiving, he has added 65 receptions for 587 yards and five touchdowns through the air.
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Isaac Guerendo
Guerendo was a fourth-round pick by the 49ers in the 2024 NFL Draft. With McCaffrey sidelined, he played in all 16 games as a rookie, averaging five yards per carry and totaling 420 yards on 84 carries, with four rushing touchdowns.
Having seen significant action, Guerendo is familiar with the playbook and has performed well. That experience likely makes him part of a split backfield against the Seahawks in Week 1.
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Who will start if McCaffrey is inactive in Week 1?
If McCaffrey does get ruled out for Week 1, the 49ers will likely deploy a split backfield. Guerendo has the benefit of experience with San Francisco, but Robinson has more experience playing in the NFL.
The 49ers also traded for Robinson, which could mean that they didn't feel as confident with Guerendo being the direct backup. Both running backs will likely see plenty of action against the Seahawks on Sunday afternoon. If you had to pick one of them, though, like for fantasy football, even though he is newer to the team, Robinson is likely the better choice.