Edwards-Helaire, who entered the game as the Chiefs' leading rusher with 291 yards, was helped off the field by teammates after getting tackled following a screen pass with 8:08 remaining in the third quarter.
After a brief examination on the sideline, he was escorted by medical personnel to the locker room.
Edwards-Helaire finished with 13 yards on seven carries and one catch for 11 yards after back-to-back 100-yard rushing games.
Chiefs coach Andy Reid didn't give an update on Edwards-Helaire after the game.
Tight end Travis Kelce also left in the closing minutes of the fourth quarter after taking a blow to the head on an incomplete pass. Reid called it a "stinger," and said receiver Tyreek Hill also injured his knee.
The Associated Press contributed to this report.