Isaac Guerendo — 2026 Fantasy Outlook

Guerendo never got a real chance to carry the load at Wisconsin, totaling just 119 touches over five seasons for 706 combined yards, seven touchdowns, and 20 catches. Hamstring trouble and a foot injury ate into his availability across three of those years. A transfer to Louisville finally unlocked his opportunity, producing a breakout 2023 season (132 carries for 810 yards and 11 touchdowns, plus 22 catches for 234 yards).

San Francisco selected him in the fourth round of the 2024 draft. His 4.33 40-yard dash at the combine confirmed what the tape suggested — Guerendo’s a plus athlete who plays with physicality and intent. He's also a capable pass protector and a reliable target out of the backfield, giving him a well-rounded skill set that can grow further as long as he stays on the field. That last part is the key caveat.

Injuries to the 49ers' backfield gave Guerendo openings he wouldn't have otherwise seen as a rookie, and he made the most of them in four outings — 10/99, 102 combined yards with a touchdown and three catches, 15/78/2 with two catches for 50 yards, and 75 combined yards with four receptions. The problem is he also missed time with foot, hamstring, and knee issues, which is a familiar pattern given how often injuries derailed him in college. Health remains the defining question around his outlook.

San Francisco barely used an RB3 option last year, leading to Guerendo getting no snaps, with his only injury (shoulder) coming last August. His lack of chances was tied to Christian McCaffrey and Brian Robinson staying healthy all year.