Hardesty injured his calf in the first half of a 20-10 loss at San Francisco on Sunday running a route and did not return.
He is scheduled to have an MRI on Monday, but said the injury does not appear serious. Hardesty was walking around the Browns locker room after the game.
Cleveland already was without starter Peyton Hillis, who missed his second straight game with a strained left hamstring. Hillis had been questionable to play but made the trip to San Francisco hoping his hamstring would improve.
Hardesty finished with two rushes for 6 yards. Chris Ogbonnaya replaced Hardesty.