A season that began on the injured list could end the same way for San Francisco 49ers star running back Christian McCaffrey.

After McCaffrey left in the second quarter of the 49ers’ 35-10 loss at Buffalo in Week 13 on Sunday night and never returned, San Francisco coach Kyle Shanahan told reporters that he had injured the posterior cruciate ligament in his knee. With five games remaining on the schedule, McCaffrey’s injury could be season-ending, Shanahan added.

McCaffrey will reportedly undergo an MRI on Monday.

With 11:23 left in the second quarter, McCaffrey took a throw and ran to his right, but immediately appeared to hobble and slip rather than be hit. It was unclear whether that play caused the injury.

Sunday’s game was the third that McCaffrey played after missing the first eight games of this season because of Achilles tendonitis in both legs. He had reportedly traveled to Germany to receive treatment on his legs.

McCaffrey’s father Ed, the former Super Bowl-winning receiver, said on a podcast that the tendonitis was an “overtraining injury.”

“If I would say Christian has a weakness, it is that sometimes he has to protect himself from himself by training too much and doing too much,” Ed McCaffrey said on the “Ross Tucker Football Podcast” in October.

Losing McCaffrey at the start and potentially the end of the season is a huge blow. He was the 2023 NFL Offensive Player of the Year, and his ability to run and catch passes out of the backfield made the 49ers the NFL’s leader in yards per offensive play and second in points per game last season.

Although injuries to other San Francisco standouts, including receivers Brandon Aiyuk and Deebo Samuel and tight end George Kittle, hampered the 49ers’ start this season, McCaffrey’s absence eliminated one of the league’s most dynamic threats, whose seriousness as defenses paid him attention dedicated, openings were regularly created for teammates. Without McCaffrey for most of the season, the 49ers have stumbled to a 5-7 record.