The San Francisco 49ers' running back situation has gone from bad to worse following their 35-10 loss to the Buffalo Bills. Not only is Christian McCaffrey out for the season with a PCL injury, but his backup, Jordan Mason, will also miss significant time with a high-ankle sprain. This leaves rookie Isaac Guerendo as the likely starter for the remainder of the season.

The news of McCaffrey's injury was confirmed shortly after the game, with 49ers head coach Kyle Shanahan initially suggesting a potential multi-week absence. However, the diagnosis revealed a six-week recovery period, effectively ending McCaffrey's season with only five games left to play.

San Francisco 49ers running back Jordan Mason is shown during the first half against the Buffalo Bills on Dec. 1, 2024. (IMAGN)

The loss of Mason further compounds the 49ers' woes. He had stepped up admirably earlier in the season when McCaffrey was sidelined with Achilles tendinitis, exceeding 100 rushing yards in three of his first four starts. He has accumulated 789 rushing yards and three touchdowns this season, significantly surpassing his previous career highs.

With their top two running backs out, the 49ers are now turning to Guerendo, a fourth-round pick from Louisville. While he has shown flashes of potential, rushing for 246 yards and two touchdowns on 42 attempts in 12 games, the rookie now faces the immense pressure of leading the 49ers' rushing attack as they fight for a playoff spot.

San Francisco 49ers running back Christian McCaffrey runs with the ball during the first half against the Buffalo Bills on Dec. 1, 2024. (AP Photo/Adrian Kraus)

At 5-7, the 49ers face an uphill battle to make the playoffs. The team has now lost three consecutive games and sits at the bottom of the NFC West. Given the importance of the run game in Shanahan's offensive scheme, the loss of McCaffrey and Mason deals a significant blow to their playoff hopes.

San Francisco 49ers running back Jordan Mason runs with the ball in the third quarter against the Buffalo Bills. (Mark Konezny-Imagn Images)

McCaffrey's brief appearance in the game saw him gain 53 rushing yards on seven carries and add two receptions for 14 yards before exiting with the injury. This season has been plagued by injuries for McCaffrey, limiting him to just four games.