His agent Dave Bradley confirmed that the actor died on Friday evening of liver and kidney failure, reported Entertainment Weekly.
Earlier, Lester was transported from an intensive care unit at a Dallas-area hospital into hospice care.
Lester has been in the hospital for four months. The actor spoke publicly about his liver and kidney issues on Twitter back in November.
"Liver & kidneys are starting to heal, Came close to dying! With out my fiance Jennifer Worland, I wouldn't be alive!"
Lester appeared as the large offensive linemen in the high school football film and parodied the character in "Not Another Teen Movie".
Once weighing 508 pounds, Lester dropped to under 200 pounds (as of 2014) after receiving gastric bypass surgery in 2000.
