Rhule said he did not immediately know the extent of the injury for McCaffrey, who missed 13 games last season with injuries and five games this season with a hamstring injury.
McCaffrey saw his streak of catching at least one pass in 57 consecutive games in which he has played snapped.
The Panthers gave up five sacks, but only one of those was on Newton.
The Panthers are 0-2 with Newton as the starter, but until Sunday his performance had been solid.
Newton’s poor performance came less than three weeks after he was signed to a one-year deal that could pay him up to $10 million for the rest of the season if he meets incentives.
“Today, it really got exposed because of the situation, not having a full grasp,” Newton said.