The San Francisco 49ers will be without their top two running backs for the foreseeable future.

Starter Christian McCaffrey will be placed on injured reserve due to a PCL injury in his right knee and top backup Jordan Mason is headed to IR with a high ankle sprain, coach Kyle Shanahan announced Monday.

McCaffrey’s injury carries an expected six-week recovery period. He will not need surgery, Shanahan said.

Rookie Isaac Guerendo will now assume the starting duties for the 49ers, who dropped into last place in the NFC West at 5-7 after their loss Sunday night to the Buffalo Bills.

Sunday night was just McCaffrey’s fourth game since returning from the bilateral Achilles tendinitis that kept him out for most of training camp and all of San Francisco’s first eight games. He rushed for 53 yards on seven carries before leaving with his injury Sunday night.

Mason capably filled in for McCaffrey while he was out Sunday night. He finished with 13 carries for 78 yards, and Guerendo scored the Niners’ lone touchdown of the night, bursting off the left side from 15 yards out.

Mason leads the 49ers in rushing this season with 789 yards and has scored three touchdowns while McCaffrey has 202 yards in his abbreviated action. He hasn’t scored a touchdown in four games after scoring 21 total touchdowns in 2023.