McCaffrey had 19 rushes for 59 yards and two touchdowns and four catches before the injury, which occurred during a 7-yard touchdown run. He walked off the field with a limp after the touchdown and did not return.
Coach Matt Rhule said after the loss to the Buccaneers that all he knew about McCaffrey's situation is he came out with what trainers called a "lower leg injury.''
Rhule did not know if it was related to McCaffrey taking himself out of the game in the first quarter on a third-down play.
McCaffrey is coming off a 2019 season in which he became the third player in NFL history to have 1,000 yards rushing and receiving in the same season.
Mike Davis finished as Carolina's primary back.