Peyton Manning, one of the NFL's biggest names, underwent neck surgery that threatens his season, hours before the league's first game of 2011 kicked off.
The Indianapolis Colts said the four-time MVP will need up to three months to recover and it was not clear whether he will be able to play at all this season.
The 35-year-old quarterback, the game's highest-paid player, had an earlier neck operation on May 23, had not recovered and was unable to practice. After two days of speculation and reports based on unnamed sources, ESPN confirmed that Manning underwent cervical fusion surgery on Thursday.
Manning's father, himself a former NFL quarterback, said Peyton Manning tried to rehab after the first operation, but fell short. On Sunday, his string of 227 starts in a row will end.
"I think he's OK, probably because there's a little finality to this deal in terms of playing," the elder Manning told ESPN's Chris Mortensen. "He's been on the clock since May. He didn't make it. Obviously, it's a big letdown, but he can relax a little bit compared to the intensity of everything he has done trying to rehab."
The team did not place him on injured reserve, which would have ended his season. Instead, Colts officials said Manning is out for 2-3 months.
Earlier this month, the Colts, known for their complicated offensive playbook, brought longtime veteran Kerry Collins out of retirement to call the signals. With Manning out, it will likely be up to Collins to run the team for at least the first half of the season.