Lester was moved from the intensive care unit to hospice care in a Dallas hospital Friday.
Bradley later confirmed on his Facebook page that the actor had died on Friday evening.
"Tonight my friends we lost my good friend and actor Ron Lester - he passed at 8:57 pm Dallas TX Time. He was not in any pain and passed away peacefully," he wrote.
"For the media - I will release a press statement as soon as I have a chance to mourn my friend. Please keep his fiancee Jennifer Worland in your prayers as she was with him. His friends and family was around him during this difficult time."
Lester's agent, Dave Bradley, told the Associated Press on Saturday that Lester had been hospitalized since February due to liver and kidney problems. Bradley also told AP that Lester died Friday after he was removed from a ventilator.
The Georgia-born actor was previously admitted to hospital in November (15) due to liver and kidney issues.
"Liver & kidneys are starting to heal, Came close to dying! With out my fiancé (sic) Jennifer Worland, I wouldn't be alive," he wrote on Twitter alongside a photo of the pair kissing.
Lester grew up in Georgia, the son of a truck driver and artist. He began his acting career by portraying 'Spatch' in the popular Nickelodeon Movie Good Burger in 1997.
He followed that up playing the large offensive lineman Billy Bob in 1999's Varsity Blues. The lumbering player stood out for his comedy, complexity, and for scoring the game-winning touchdown in the District Championship Game. The gig followed closely to real life for Lester.
"I had the same feelings that my character had," he told Movieweb earlier this year. "Jon Voight is like a father figure to me, and after doing this movie, he's just the greatest mentor I had. There were times, like in those scenes where he was chewing me out, I allowed the emotion to come out, because it was real. The only thing I really had to act was the lines."
He later starred on The WB show Popular for its two seasons. After spoofing his Varsity Blues character in Not Another Teen Movie, this time named Reggie Ray. Lester did not appear in another major studio film.
More recently he made an appearance on CSI: NY, and had a part in the upcoming film Bomb City.
At his heaviest, Lester was 508 lbs. He underwent gastric bypass surgery - and flatlined on the operating table - in December 2000, according to a 2014 interview with Grantland. He lost over 300 lbs., including 100 lbs. in the ensuing month-and-a-half after surgery.
In the years following, he talked about the decision to have the surgery in bittersweet terms, telling BodyBuilding.com that he was rebuilding his career: "The difference is that I am no longer the 'funny fat guy,'" Lester said. "I sold my 'niche' for my chance to live. ... I would never trade the life I have now with... the endless opportunities I have in store for me, with my old life."
In his final months, Lester was working on his racing and coming-of-age movie, Racing Legacy, that he starred in, co-directed, and wrote.
Lester is survived by his fiancée, Jennifer Worland.
You can read Nickelodeon Magazine's short interview with the cast of Good Burger, including Ron Lester, here on the Nickelodeon Ooze News Archive.
NickALive!'s thoughts go out to Ron's family and friends during this difficult time.
Additional sources: Ron Lester's official MySpace profile page, RTÉ Entertainment, E! Online, The Hollywood Reporter.