Entering 2025, San Francisco 49ers second-year running back Isaac Guerendo might have been a name to watch among fantasy football fans.
After all, the Niners cleaned house during the offseason, executing a swarm of moves that depleted their offense, including trading their top rusher from 2024, Jordan Mason, to the Minnesota Vikings.
In theory, this bumped Guerendo up the depth chart to No. 2 behind All-Pro Christian McCaffrey, whose own injury concerns mandated fantasy owners have some sort of handcuff or contingency plan in place.
After all, the fourth-round draftee out of Louisville became a primary beneficiary amid McCaffrey's injuries in 2024 that limited him to just four games played, and Guerendo responded with a solid 420-yard, four-touchdown rookie year that saw him average 5 yards per carry. Tack on 15 catches for 152 yards, and it's easy to see why he'd be worthy of a late-round pick despite his own shoulder concerns.
But the context has changed. Big time.
Isaac Guerendo's fantasy value hits new low amid 49ers depth chart release
Guerendo did himself no favors during the preseason by suffering another shoulder injury, and further shortages at running back prompted San Francisco to execute a trade with the Washington Commanders for running back Brian Robinson Jr.
Not long thereafter, head coach Kyle Shanahan all but confirmed Robinson would be the No. 2 tailback behind McCaffrey, thereby relegating Guerendo to a tertiary role, at best.
Then, on Tuesday before the 49ers' regular-season opener against the Seattle Seahawks, the release of an unofficial depth chart backed up Shanahan's statements on both Robinson and Guerendo, listing them as RB2 and RB3, respectively.
As a result, ESPN leagues responded by de-rostering Guerendo by 7.8 percent, and he's now down to being rostered in just 7.9 percent of leagues.
But, there's a catch.
Isaac Guerendo remains worthy of a watch list
Guerendo probably isn't worth a spot on a fantasy roster at this point, even in deeper leagues. However, it doesn't take much to accept the fact the Niners have all kinds of bad luck getting running backs injured, and the 29-year-old McCaffrey is one of the bigger injury risks out there entering 2025.
Last year's injury attrition at running back appeared to spill over into the preseason last August, too, with Ameer Abdullah and Patrick Taylor Jr. both winding up on season-ending injured reserve.
Therefore, it's probably a reasonable bet McCaffrey misses at least a few games in 2025, meaning Guerendo's value as a handcuff should increase, even if only in a modest fashion.
Should San Francisco endure another year of getting running backs injured, Guerendo's value will skyrocket once again, meaning fantasy football owners shouldn't hesitate to at least place a watch on the second-year pro out of Louisville in case the door opens for him to make another unexpected impact.