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Will Isaac Guerendo play for the San Francisco 49ers in 2025? Will Isaac Guerendo be healthy enough to play in Week 1? John breaks down the latest Isaac Guerendo injury news for fantasy football.
San Francisco 49ers running back Isaac Guerendo (shoulder) had a promising rookie campaign in 2024, playing in relief of starting running back Christian McCaffrey. In the freshman's first game playing over 50 percent of the snaps, he scored 19.20 PPR fantasy points.
He played just three more games with over half the offensive snaps, and racked up 26.8, 11.5, and 13.9 PPR points. Though these were impressive overall numbers, he also suffered from injuries later in the season. He's also currently dealing with a shoulder issue.
Guerendo clearly has a ton of potential, but it's questionable if he'll be able to take the field. Add in that McCaffrey has (supposedly) returned to full health, and that the team's backfield has a lot of competition, and it's unclear how things will shake out. So let's break it all down!
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Will Guerendo Play This Season?
Yes. Though his shoulder is hurt, he played through that injury in the team's final preseason game, rushing eight times for 13 yards and catching a single pass for one yard in the contest against the Los Angeles Chargers. Guerendo solidified himself as a strong backup, and though he's still on the injury report, we saw him on the field.
Isaac Guerendo on preseason punt coverage with a bad shoulder is pretty maddening https://t.co/Nl3CJwmqrI
— Hayden Winks (@HaydenWinks) August 24, 2025
Of course, the major question here is... why is he playing? It's unclear how the 49ers manage their injuries. Last season, we saw running back Jordan Mason enter a game with a shoulder injury, play, and almost immediately get knocked out of the game after re-aggravating his shoulder.
It seems that head coach Kyle Shanahan wants to control which personnel play on which play with an iron fist. Unfortunately, this has led to the team typically dealing with numerous injuries throughout the regular season.
Thus, it's tough for me to trust Guerendo staying healthy for the season. He should play, obviously, but at this point, expecting every 49ers player to miss at least some time is likely the safest bet to make. They constantly have multiple star players dealing with major ailments.
Will Isaac Guerendo Play In Week 1?
Considering that he played in the preseason game, the answer to this is also likely yes.
And considering how Shanahan likes to use his top running back, it's unlikely that Guerendo will re-aggravate his injury, unless he's used on special teams, which seems like a possibility, considering he played ST snaps in the preseason.
Isaac Guerendo -
Appears to aggravate his Right shoulder. Brace and mechanism still make me think labral involved.
We’ll see, but this is why SF traded for BRob.Note: Guerendo fumbled 3 times in his first practice back. The shoulder wasn’t 100%.
pic.twitter.com/mj4o0wGOdy— Jeff Mueller, PT, DPT (@jmthrivept) August 24, 2025
Considering he fumbled three times in practice and carries the ball in his right arm, which is the shoulder that's injured, perhaps Shanahan won't have him carry the ball much. But if he's playing in the preseason, you have to assume he suits up for Week 1.
Isaac Guerendo 2025 Fantasy Outlook
Guerendo is a tough player for me to draft at the moment. He may get a significant workload right away if McCaffrey gets injured, and I'm usually a proponent of taking cheap players with considerable upside, even if they're injury-prone. I've simply been throwing other darts in the late rounds.
The 49ers traded for RB Brian Robinson Jr. from the Washington Commanders recently. It's possible that Guerendo could be held out of games and Robinson could be the starter if McCaffrey goes down, which would leave Guerendo with very little utility.
Brian Robinson burned the Lions in the divisional round with 2 scores. He’s been very productive in three years. New weapon for Kyle Shanahan and the #49ers. pic.twitter.com/wGA2IDrbZA
— Matt Lively (@mattblively) August 22, 2025
The Robinson trade only makes sense to me if San Francisco thinks none of their other backs will be fully healthy in Week 1, and even more so if injuries remain an issue for this position group. Shanahan isn't known for having committee backfields, but I worry that Guerendo could struggle to find consistent playing time due to his injury history.
He had major injury red flags in college and missed substantial time with ailments. The same seems to be happening in the NFL, and the 49ers seem to be the worst team to have to deal with this as a fantasy manager. If you draft McCaffrey, I like Guerendo as a very late-round dart throw, but not much more.
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