The star back was put on a cart and taken from the sideline to the locker room.
If Barkley is unable to return, Dion Lewis will take on the majority of the workload.
Barkley had the second-worst rushing performance of his young career in Week 1, finishing the loss to the Pittsburgh Steelers with just six yards on 15 carries.
The former No. 2 overall pick is the key cog of New York's offense, and missing any time would be a devastating blow to the team.