The Buccaneers announced Friday that Nicks and the team have "mutually agreed that they will part ways."
"I'd like to thank the Buccaneers organization for working with me as I have attempted to get myself back on the football field," Nicks said in a press release distributed by the team. "However, after careful consideration, I have made the decision to step away from the game. This was by no means an easy decision, but I believe that it is what is best for me and my family as well as the Tampa Bay Buccaneers."
Nicks' career took a sudden downturn after he suffered a toe injury that led to a dangerous MRSA infection. He played in only two games last season and missed the Bucs' entire offseason program. He had been medically cleared for training camp before Friday's announcement.
Nicks signed a five-year, $47.5 million contract with the Bucs in March 2012. The deal included $31 million guaranteed.
"I know this has been a difficult time for Carl and his family, but we respect his decision and thank him for his effort in trying to get back on the football field," Buccaneers general manager Jason Licht said. "Carl is a very prideful athlete and has been an elite level guard in the league. We are all disappointed that he will not be a part of this new chapter of Buccaneers football."
It remains to be seen if Nicks' decision to "step away from the game" means retirement. If so, Nicks leaves the league at age 29.