James, who rushed for 158 yards against the Seattle Seahawks in Week 9, was starting the third game of his NFL career on Monday night. A sixth-round pick in the 2013 NFL Draft, James had rushed five times for 41 yards on Tampa Bay's opening drive before being taken down awkwardly and twisting his ankle.
James needed to be helped to his feet and was taken to the locker room on a cart. With Buccaneers starting running back Doug Martin already out for the season with a shoulder injury, Brian Leonard and Bobby Rainey are the next two running backs on the team's depth chart.
James is questionable to return to the game.
UPDATE: James has been officially ruled out for the game.