But the superstar quarterback's medical problems -- an infected bursa sac in his left knee -- only adds to the long injury list the Indianapolis Colts will face when they open training camp July 25.
Not only will Manning be unavailable, but so will defensive end Dwight Freeney, wide receiver Marvin Harrison and safety Bob Sanders, the NFL's Defensive Player of the Year last season.
The Colts said Manning can make a "full and complete return" in four to six weeks. That means, at worst, he can open the season against Chicago the night of Sept. 7, when the Colts unveil their new stadium in a replay of the 2007 Super Bowl. Given Manning's durability, there's a chance he could play the last exhibition game or two.
"There is no sense of any untoward condition with this," team president Bill Polian told The Associated Press on Tuesday.
Still, it leaves the Colts with Jim Sorgi as the only experienced quarterback when the team goes to training camp.
Also on the roster are Josh Betts, Ben Roethlisberger's backup at Miami of Ohio, who spent last season on the practice squad, and Adam Trafalis, an undrafted rookie from San Jose State. Polian said he will not sign another quarterback.
A bursa sac provides a cushion between bones and tendons around most major joints in the body. They can become inflamed, which is what happened to Manning.
Manning has started every game in the 10 years he's played in the NFL, with his consecutive starts second to Brett Favre's 253. If Favre makes good on his intended desire to return, his streak could be extended -- or broken.
"I'm going into my 11th year. I'm 32, but I really feel I'm in a younger body than that," Manning said last week. "I feel I'm in a 28-year-old body because I've had great protection from my offensive line. I feel that's hopefully going to allow me to play a number of more years."
Another injured Colt is starting linebacker Tyjuan Hagler, who has a torn pectoral muscle and is expected to start camp on the physically unable to perform list.
So are Harrison, Sanders and Freeney.
Harrison, 35, appears to be of the most concern. He missed most of last season with knee problems, including one with a bursa sac. He had arthroscopic surgery on his right knee in January and has been rehabilitating an inflamed left knee.
Freeney had surgery after a season-ending injury to his left foot last November. Polian said the only question is his conditioning level.
Sanders had shoulder surgery in the off-season.