Head coach Matt Rhule told the media he does not expect McCaffrey to play Sunday against the Denver Broncos but will continue to monitor his health.
McCaffrey tweaked his quad during the team's bye week, according to Rhule, and it flared up Wednesday, limiting him in practice.
McCaffrey has played in just three of the Panther's 12 games this season but has scored six touchdowns.
After suffering a high-ankle sprain in Week 2 at Tampa Bay, McCaffrey was placed on injured reserve, missing six-straight games.
He returned Nov. 8 at Kansas City, but injured his shoulder in the fourth quarter, forcing him to miss three more games.
In 2019, McCaffrey became just the third player in NFL history to have 1,000 rushing yards and 1,000 receiving yards in the same season.