Losing to the Kansas City Chiefs for the fourth straight time, including two Super Bowl defeats, wasn’t the only setback for the San Francisco 49ers on Sunday afternoon at Levi’s Stadium.

Running back Brandon Aiyuk exited the game with time ticking down in the first half with a lower-body injury. After taking a pass from quarterback Brock Purdy, Aiyuk was crunched between Justin Reid and Chamarri Conner; replays showed his right leg hitting the ground awkwardly.

He managed to limp off the field but was barely able to put any weight on his leg. After a short stay in the blue medical tent, he was carted off to the locker room and did not return. And according to head coach Kyle Shanahan, the team fears the injury could be season-ending, via X:

“Brandon Aiyuk had a knee, we're worried it's an ACL,” he explained. It's not confirmed yet, but we'll find out for sure tomorrow.”

Before the injury, he had two catches for 23 yards. The 49ers were eventually defeated by a 28-18 final score, dropping them to 3-4 through seven games while the Chiefs remained undefeated at a perfect 6-0.

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Aiyuk missed all of Training Camp, holding out for a larger contract before the two sides eventually settled on a four-year, $120 million extension with over $70 million of it guaranteed.

So far this season, he's been targeted 47 times while racking up 374 receiving yards on 25 catches and no touchdowns.

It's the latest injury setback for the 49ers, who were already without the services of Christian McCaffrey due to an Achilles ailment along with leading receiver Jauan Jenning.

Unfortunately for the 49ers, the schedule does not pause to allow players to heal and recuperate. They'll have to take the field without Aiyuk and several other key players when they host the rival Dallas Cowboys next Sunday at Levi Stadium.