Pierre-Paul missed practice on Wednesday with his back issue. The defensive end has had back spasms in the past.
"He is not going to play in this game in all likelihood," coach Tom Coughlin said. "I just think it will end up being precautionary based on what we had to do today by not letting him work.
"He would have practiced and played. But the medical people said this would be the best way to go, so we ensure going forward he will be OK."
Osi Umenyiora will start opposite Justin Tuck if Pierre-Paul doesn't play. The Giants have several other injuries they are dealing with. Left tackle Will Beatty continues to be out with a back injury. Linebacker Michael Boley has been out with a hamstring injury, and backup defensive end Adrian Tracy has been sidelined by a hamstring injury. Defensive tackle Shaun Rogers (blood clot) and cornerback Terrell Thomas (knee) are out indefinitely as well.
Cornerback Jayron Hosley (turf toe), defensive tackle Marvin Austin (back) and offensive tackle Brandon Mosley (ankle) will also miss Friday's game. Defensive tackle Chris Canty (knee) and tight end Travis Beckum (knee) remain on the physically unable to perform list.
Backup safety Will Hill missed practice on Wednesday because of a death in the family but is expected to play against the Bears.