Perine was hit and fumbled with 5:51 left in the third quarter. A hush fell over the crowd as he remained on the ground after the play. He got up and put pressure on his right leg as he was helped off the field. An Oklahoma medical staff member put ice around Perine's left ankle once he went to the sideline.
Perine, who set the major college record for yards rushing in a game two weeks ago with 427 yards against Kansas, left Saturday's game with 26 carries for 151 yards and two touchdowns.
No. 18 Oklahoma led 28-14 when the injury occurred.