SANTA CLARA — San Francisco 49ers star running back Christian McCaffrey will not need surgery on his injured right knee but he will miss the rest of the regular season.

Coach Kyle Shanahan said Monday that McCaffrey will be out at least six weeks after injuring his posterior cruciate ligament in a loss to the Buffalo Bills on Sunday night. McCaffrey will be placed on injured reserve for the second time this season after previously missing the first eight games with Achilles tendinitis.

“I just feel for him,” Shanahan said. “It was a real frustrating year for him. He worked his ass off to get back to this point and I think he was really feeling good and about to take off and just had that real unfortunate injury last night. I know he’s as crushed as anyone, but he’ll get through this. He’s a hell of a player, a hell of a person and an unbelievable 49er. He’ll be back stronger than ever next year to help us.”

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49ers Struggle Without McCaffrey

San Francisco (5-7) sits alone in last place in the NFC West standings, two wins behind division-leading Seattle, and in jeopardy of missing the playoffs a year after losing to Kansas City in the Super Bowl.

The 49ers also lost McCaffrey’s backup to an injury with Jordan Mason also set to go on injured reserve after suffering a high ankle sprain in the game against the Bills.

It has been a frustrating season for McCaffrey, who won the 2023 AP Offensive Player of the Year then signed a lucrative contract extension in the offseason.

McCaffrey injured his Achilles tendon early in training camp and missed the first eight games of the season. He rushed for just 149 yards on 43 carries in his first three games back as he struggled to get back to form.

He looked much better early Sunday night with seven carries for 53 yards, including a 19-yarder that was his longest of the season. He appeared to hurt his knee on an 18-yard run in the second quarter. He then went down immediately on his next carry on a sweep to the left on a snow-slicked field for a 5-yard loss.

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49ers Turn to Rookie Running Back

Mason had played well as McCaffrey’s replacement, rushing for 789 yards and averaging 5.2 yards per carry this season.

San Francisco will now turn to rookie Isaac Guerendo and promote Patrick Taylor from the practice squad. Shanahan said the team will also look to add another running back to the mix.

In other injury news from the game, defensive lineman Kevin Givens tore his pectoral muscle and will be out for the rest of the season.

Shanahan said cornerback Deommodore Lenoir should be back at practice Wednesday after missing the game with a knee injury and that stars Nick Bosa (hip, oblique) and Trent Williams (ankle) will be evaluated as the week goes on.

Bosa and Williams have both missed the last two games. Williams has also been dealing with family tragedy as his wife announced on Instagram that she gave birth to stillborn Trenton O’Brien Williams Jr. on Nov. 24. Sondra Williams also wrote that she was initially pregnant with twins and lost the other child earlier in the pregnancy.

Shanahan said Williams spent time with his family last week but is trying to get back to play.

“He was there at the hospital with her and got to meet him and say bye,” Shanahan said. “Then he had to cremate him on Friday. So he’s been dealing with that and he’s working through it. We’re all just trying to be there for him through it all.”

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49ers Injury Updates

NOTES: OL Aaron Banks and DT Jordan Elliott remain in the concussion protocol. … LB Demetrius Flannigan-Fowles (knee) is day to day. … LB Dre Greenlaw will get more work this week after his practice window was opened last week for the first time since he tore his Achilles in the Super Bowl. … S Talanoa Hufanga (wrist) will have his IR practice window opened this week.