Kamara carried the ball 10 times for 45 yards in the first quarter but went to the locker room and did not return to play in the second quarter. Backup running back Jamaal Williams took Kamara's place, with Kendre Miller ruled out before the game.
"He sprained his ankle, I think it was on the sideline over there ... in the first half, right before the end of the half, when he got tackled on their sideline over there," coach Dennis Allen said after his team's victory. "Kind of came in, got it looked at, came out after the half to try to test it out and just didn't feel like he was going to be able to be functional enough to help us win."
Allen said he doesn't know if it's a high ankle sprain.
Kamara was the third Saints player ruled out of the game. Offensive lineman Landon Young (knee) and linebacker Nephi Sewell (knee) both left with injuries and did not return. Tight end Juwan Johnson briefly left with a shoulder injury but returned to the lineup.
Before Kamara left with the injury, he became the first player in franchise history to hit the 10,000 career yards from scrimmage mark.
The Saints play the Atlanta Falcons at home next week for their regular-season finale and are still alive for the NFC South title.