Isaac Guerendo emerged as a key fantasy football option for the San Francisco 49ers last season amid several injuries in the running back corps. With Christian McCaffrey limited to just four games due to injuries, Guerendo stepped in as the lead running back in several contests, delivering strong fantasy performances. As fantasy managers consider the 2025 season, questions remain about whether Guerendo is a reliable draft pick or a risky handcuff dependent on McCaffrey’s availability.
Originally a lesser-known Day 3 draft pick, Guerendo impressed with his elite speed, posting a 4.33-second 40-yard dash at 221 pounds, a figure placing him in the top percentile for speed among NFL running backs. Despite his athletic potential, Guerendo started the season buried behind McCaffrey, Elijah Mitchell, and Jordan Mason on the depth chart.
How Injuries Opened Doors for Guerendo Last Season
The 49ers‘ running back situation was heavily impacted by injuries throughout last season. Elijah Mitchell suffered a season-ending injury during training camp, while McCaffrey played only four games before another injury sidelined him. Jordan Mason also faced setbacks, with injuries limiting his availability and forcing the team to rely on Guerendo more extensively.
Guerendo assumed lead back duties in four games, producing fantasy point totals of 19.2, 26.8, 11.5, and 13.9, averaging 17.85 points per game—numbers consistent with a top-tier running back in fantasy leagues. This surge established Guerendo as a trusted backup and insurance policy behind McCaffrey.
Following the season, the 49ers released Mitchell and Mason, effectively elevating Guerendo to the primary backup role. His spot as RB2 seems secure, though the team also drafted Jordan James in the sixth round, who could contribute but is not expected to challenge Guerendo’s secondary role.
Assessing McCaffrey’s Durability and Guerendo’s Fantasy Value
Christian McCaffrey enters his ninth NFL season with a well-documented history of injuries affecting his playing time. He typically either participates fully or misses significant chunks of the season, having played seven or fewer games during his three injury-plagued seasons. This pattern suggests that a running back on the 49ers roster is unlikely to have substantial fantasy impact alongside McCaffrey when he is healthy.
For fantasy managers, drafting Isaac Guerendo is largely an injury-dependent play. He holds an average draft position of RB45 but carries the upside of a true RB1 if McCaffrey misses time. Guerendo is ranked RB44 by some experts, placing him among several running backs who serve as valuable handcuffs rather than standalone starters.
Frank Ammirante’s Perspective on Guerendo’s Fantasy Projection
Fantasy analyst Frank Ammirante rates Guerendo as a solid handcuff running back with demonstrated upside in limited action last season, including a notable performance versus the Bears where he accumulated 128 total yards and scored two touchdowns.
As McCaffrey’s backup, Guerendo is best considered a high-upside stash for fantasy rosters rather than a player to rely on independently. Ammirante advises that the San Francisco star will continue to dominate the team‘s workload barring injury.
However, Guerendo’s current camp leg injury introduces uncertainty early in the season, simultaneously creating a potential opportunity for managers to acquire him at a reduced price due to concerns about his availability.
Ammirante cautions fantasy owners to limit the number of non-starting handcuffs on their bench to maintain roster flexibility for weeks when these players do not produce.
Implications for Fantasy Managers Ahead of the 2025 Season
Isaac Guerendo represents a classic high-risk, high-reward option for fantasy teams targeting the 49ers’ backfield in 2025. His demonstrated ability to perform at an RB1 level when called upon offers valuable insurance behind McCaffrey, but that value hinges entirely on McCaffrey’s health.
Fantasy managers must weigh Guerendo’s explosive speed and past production against his lack of consistent usage and injury questions. Given the 49ers’ roster decisions and McCaffrey’s injury history, Guerendo could be a pivotal asset if injuries arise or remain a lower-tier backup otherwise.
Ultimately, including Guerendo on fantasy rosters could pay off handsomely for those willing to draft him as a handcuff, but it requires careful allocation of bench spots to balance upside potential with week-to-week usability in a demanding season ahead.