With both Hakeem Nicks, pictured left, and Ahmad Bradshaw out, the Giants will be missing a tandem that has combined for a significant portion of the team's offense since they became teammates.
Bradshaw, Nicks Since 2009
Yards From Scrimmage
-- ESPN Stats & Information
The Panthers, meanwhile, will be without running back Jonathan Stewart for the second straight week. Stewart's toe and ankle are bothering him and he will sit out again.
Nicks initially was questionable for the game earlier on Wednesday but was downgraded and did not make the trip.
Nicks did not participate in any of the team's workouts this week, including Wednesday morning. Tom Coughlin said Nicks sat out Tuesday's practice as a planned day of rest.
Nicks is the fourth prominent Giants player to be ruled out for Thursday's game. The team also will be without running back Ahmad Bradshaw, offensive tackle David Diehl and wide receiver Domenik Hixon.
Rookie defensive end Adewale Ojomo also will not make the trip to Charlotte.
After Nicks was not able to do much Wednesday morning, the team opted to play it safe with the receiver, taking into consideration there were only three days in between Sunday's game and Thursday's game against Carolina.
Nicks now will have two weeks to rest his foot between last Sunday's game and the Giants' game against Philadelphia on Sept. 30.
Hakeem Nicks earned NFC offensive player of the week honors with 10 catches, 199 yards and a TD in the Giants' victory over the Bucs.
Nicks earned NFC offensive player of the week honors with 10 catches for 199 yards and a touchdown in the Giants' 41-34 win over Tampa Bay. But Nicks, who had surgery to repair a broken right foot in late May, did come up limping twice toward the end of that game.
Nicks said he was feeling "pretty good" on Tuesday.
"I just have to keep taking it day by day and (Wednesday) should feel a little bit better and then Thursday will be game time," Nicks said.
The Giants will be without two of their top three receivers against the Panthers. Victor Cruz will move up as the top receiver. Ramses Barden, rookie Rueben Randle and Jerrel Jernigan will have to step up for Eli Manning.
Cornerback Michael Coe has been listed as questionable for Thursday's game. Linebacker Keith Rivers and cornerback Prince Amukamara have been listed as probable -- meaning Amukamara likely will make his season debut after missing the first two weeks with a high-ankle sprain.
Bradshaw, the team's starting running back, injured his neck in the second quarter of the Giants' win and did not return. The Giants have provided no further details on his injury. Andre Brown, who performed well in Bradshaw's place -- 13 carries for 71 yards and a touchdown -- likely will get his first NFL start.
Diehl, the team's starting right tackle, injured the MCL in his right knee against the Bucs. His status beyond this week is also unknown. The Giants shifted starting left tackle Sean Locklear to right tackle and inserted Will Beatty at left tackle after Diehl went down. The same configuration is likely on Thursday night.
Hixon, the team's third wide receiver, suffered a concussion Sunday, also in the first quarter.
Panthers starting right tackle Byron Bell was ruled out against the Giants as well. Linebacker Thomas Davis also is out for Carolina.
Stewart and Bell didn't practice all week and were listed as questionable.
Garry Williams will start for Bell.
Information from The Associated Press was used in this report.