McCaffrey, dealing with a hamstring injury that kept him out of last week's 36-28 loss to the Dallas Cowboys, was listed as doubtful on Friday's injury report after practicing on a limited basis for three days.
"Nothing much more to add," coach Matt Rhule said. "He's been going. It's doubtful he'll play on Sunday. That could change. I'm not going to play any games."
Left tackle Cam Erving (neck) and linebacker Shaq Thompson (foot) were ruled out for the game on Friday's injury report. Rhule said earlier in the week that he was preparing rookie Brady Christensen or Trent Scott to replace Erving and didn't rule out moving right tackle Taylor Moton to the left side.
McCaffrey said Thursday that he "definitely" had a chance to play and felt good. But the Panthers (3-1), barring a change on Saturday or Sunday morning, are expected to err on the side of caution.
The Pro Bowl running back is likely to be ready to play next week against Minnesota.
Hubbard led Carolina with 13 carries for 57 yards against Dallas.
McCaffrey acknowledged he was frustrated by the injury after missing 13 games in 2020 with three different injuries. He said the short week before facing the Houston Texans on Sept. 23 "definitely" played a role in his injury.
"It was extremely frustrating,'' he said. "I don't prefer Thursday night games. You go through a lot in a football game. You really get two days to recover, and one of those days is a travel day.
"You hop on a plane, you're in a hotel, and you go out and play in a football game. It's really tough. It is what it is. It's part of the game."
McCaffrey in 2019 became the third player in NFL history to have 1,000 yards rushing and receiving in the same season. He entered Week 3 as the NFL's leader in total yards from scrimmage with 324 and had 364 when he strained the hamstring in the second quarter against the Texans.