The San Francisco 49ers' success in 2025 could depend heavily on the health and performance of Christian McCaffrey. The star running back endured an injury-plagued 2024 campaign, appearing in just four games and rushing for a career-low 202 yards with no touchdowns.
Now healthy, McCaffrey is looking to bounce back and return to his 2023 NFL Offensive Player of the Year form. If he can stay on the field, the 49ers' offense has a legitimate chance to reclaim its status as one of the league's most potent forces.
Bleacher Report's Moe Moton recently ranked the best running back duos heading into the 2025 season, and McCaffrey and second-year back Isaac Guerendo came in at No. 6. Moton acknowledges McCaffrey's elite talent but also points to his recent injuries—Achilles tendinitis and a PCL issue—as potential cause for concern.
The silver lining for San Francisco is Guerendo's emergence last season. With the running back room hit by injuries, Guerendo gained critical experience and proved he could contribute. That development gives the 49ers a chance to manage McCaffrey's workload and reduce his injury risk.
"So, Isaac Guerendo could have a sizeable role as the No. 2 tailback following a productive year as the third-stringer," Moton wrote. "Last year, the 24-year-old ran for 420 yards and four touchdowns, averaging five yards per carry in 16 contests. He started in three outings in place of McCaffrey and Jordan Mason."
The 49ers also added depth by selecting running back Jordan James in the fifth round of the 2025 NFL Draft. Still, Guerendo remains the clear favorite to serve as McCaffrey's primary backup after the team traded Jordan Mason to the Minnesota Vikings.
With a healthy McCaffrey and a rising Guerendo, San Francisco may boast one of the most well-rounded backfields in the NFL this season.