The team said Nicks will have surgery to repair a torn plantar plate in his left toe. The Bucs previously lost their other starting guard, Davin Joseph, to a season-ending injury in the preseason.
The Buccaneers gave Nicks a five-year, $47 million free-agent contract this offseason to lure him away from division rival New Orleans.
He has started all seven games with the Buccaneers and played in all 71 of his team's games since entering the league in 2008, including 68 consecutive starts.
Ted Larsen, at first, took Joseph's place in the starting lineup before losing the job to Jamon Meredith. Larsen, backup tackle Jeremy Trueblood and backup center Cody Wallace would be the likely internal candidates to take Nicks' starting spot at left guard. The Bucs also elevated guard Roger Allen from the practice squad on Tuesday.
The Bucs also placed backup tight end Danny Noble (hamstring) on injured reserve.
Information from The Associated Press was used in this report.