Manning underwent surgery for the third time in 19 months Thursday, a procedure that is likely to keep the four-time MVP out significantly longer than just Sunday's season opener at Houston -- the first game he will miss in 14 NFL seasons.
Team officials called Thursday's surgery "uneventful."
"The procedure is performed regularly throughout the county on persons of all walks of life, including professional football players," the team said in a statement. "Rehabilitation from such surgery is typically an involved process. Therefore, there will be no estimation of a return date at this time. We will keep Peyton on the active roster until we have a clear picture of his recovery process."
The Colts statement came just hours after team owner Jim Irsay wrote on Twitter that Manning would be out "awhile" and coach Jim Caldwell promised to provide more clarity soon. They could have put Manning on injured reserve to open up a roster spot, but that would have meant he would not play at all in a season that will end with in February with the Super Bowl played at Lucas Oil Stadium in downtown Indianapolis.
Shortly after ESPN first reported the surgery, team officials confirmed that Manning had an anterior fusion procedure to treat the nerve problem that was continuing to give him trouble.
"Peyton will immediately begin the rehabilitation regimen mapped out by the surgeon," the team said.
For Manning, one of the league's true ironmen, it was a continuation of the most frustrating offseason of his career.
He already has dealt with a 4 1/2-month lockout that prevented him from working out with team trainers after his May 23 surgery to repair a nerve. He also couldn't negotiate a new contract with the Colts during the lockout. Then he started training camp on the physically unable to perform list, which prevented him from working out with teammates until Aug. 29.
After one week of practice, left Manning with a sore back. And now surgery just one day after the Colts ruled him out of Sunday's game, ending a streak of 227 consecutive starts including the playoffs that was second only to Brett Favre among NFL quarterbacks.
The 35-year-old Manning, who signed a five-year, $90 million contract in July, also had neck surgery in February 2010.
With Manning, the Colts have been a perennial Super Bowl contender. Without him, the most dominant team in the AFC South since its creation faces a daunting challenge -- trying to become the first team to play a Super Bowl in its home stadium without having Manning behind center for what could be a significant portion of the season.
Speculation over another surgical procedure ramped up earlier this week and team owner Jim Irsay created even more buzz Thursday morning when he gave fans the latest update on Manning's condition via Twitter.
"We had a good practice yesterday and r guys r fired up 4 the season. (hash)18's out for awhile, but compete, we will/BELIEVE," Irsay tweeted.
The biggest question is when he will be back.
The Colts thought Manning would return within 6-8 weeks after surgery, but the rehab has taken far longer than anyone expected. On Monday, the team issued a statement saying his progression slowed last week, too.
"In terms of the timeframe we're talking about, I think he (Irsay) is also stating we don't know what kind of a timeframe. None of us know," Caldwell said before the surgery was announced. "It is a little bit in flux at this point."
If he does come back, Manning also will be playing behind an offensive line that has three new starters and a fourth, Ryan Diem, who is moving from right tackle to right guard.
The player who can empathize most with Manning is running back Joseph Addai, who injured a nerve in his left shoulder Oct. 17 against Washington, then missed the next eight games.
There were times, Addai recalled, that he would wake up during the night with sudden pain. There were other times that he couldn't hold up a microphone or the ball would drop out of his hands with a slight bump.
Addai figured the ensuing bye week would give him enough time to heal, but it took him more than two months to get back into a game and he still didn't feel 100 percent until this season.
"After a while it came back, but you don't really know when it's going to come back," Addai said. "It's frustrating."
Addai said Manning had asked him about the experience, something the two have discussed at length since players reported to camp July 31. Addai said he has not yet caught passes from Manning at full speed and he can't say where Manning's recovery is right now.
Instead, he's worried about playing the Texans without Manning.
"You know how important Peyton is," Addai said. "I think everybody has to step it up."
Kerry Collins is expected to replace Manning in the lineup Sunday, making him the first Colts quarterback other than Manning to start a game since Jim Harbaugh on Dec. 21, 1997.
The only other time Manning has missed a regular-season snap because of injury was in 2001 against Miami. Backup Mark Rypien fumbled. The Dolphins recovered and drove 59 yards for the winning score. Manning returned on the next series with a bloody mouth. He was later diagnosed with a hairline fracture in his jaw.
Manning, who rarely misses a snap even at practice, has occasionally been sidelined during the preseason.
He sat out one week of training camp in 1998 before signing his rookie contract. A decade later, he missed all of training camp after having surgery twice to remove an infected bursa sac from his left knee. He also missed some practices after injuring his knee during a preseason game against Minnesota in 2001.
Since being taken with the No. 1 overall pick in 2008, Manning has led the Colts to 11 playoff appearances, 11 double-digit winning seasons, eight division crowns, two AFC titles and a Super Bowl championship.