"I'm done, I'm done, that's it," Incognito told The Buffalo News. "It's been a long career. My liver and kidneys are shutting down. Nothing I can't restore with some balance, but the stress is killing me.
"I went to a doctor's appointment the other day and they said, 'Listen, the stress is killing you, what are you doing?' And I said, 'Listen, I'm just doing what I love and that's playing football.' So that's why I'm done."
Incognito, 34, sent a tweet to the NFL Players Association and its assistant executive director of external affairs George Atallah on Tuesday, saying that he was "done."
Sports Illustrated reported earlier Tuesday that Incognito was "strongly considering retiring," but might return for a final season in 2018 "at the right price."
Neither Incognito nor the Bills responded a request for comment from ESPN.
Incognito took a $1.675 million pay cut last month to remain with the Bills for the final season of a three-year contract he signed in 2016. He will now earn $4.75 million in 2018.
On Thursday, Incognito fired his agency, Athletes First, on Twitter:
"It pisses me the f--- off," Incognito told The Buffalo News about his pay cut. "The contract and all that pissed me the f--- off and all that, but (retiring) has nothing do do with that."
Asked whether there was a chance he'd change his mind, Incognito told the newspaper, "Absolutely not."
Incognito has made the Pro Bowl in each of the past three seasons after signing with the Bills in 2015. He was out of football in 2014 after being suspended by the Miami Dolphins in 2013 as part of a bullying scandal.
Bills' running back LeSean McCoy tweeted he would give Incognito $300,000 to stay with the team. McCoy ran for 1,138 yards with six touchdowns last season.
Incognito's potential retirement would mark the third high-profile departure from the Bills' offensive line this offseason. Center Eric Wood in January announced the end of his career because of a neck injury, and left tackle Cordy Glenn was traded to the Cincinnati Bengals in March.