But team officials denied reports Manning had a highly virulent form of staph infection that is difficult to treat called methicillin-resistant staphylococcus aureus (MRSA).
"At no time did he have MRSA," a team statement said.
The team, responding to reports that the staph infection prompted both of Manning's preseason left knee surgeries, said that was the case only with the first procedure, which removed the bursa sac. The second operation was to tack skin together to eliminate the space left by the removal, the team said.
The Colts, who have struggled to a 3-3 start this season, said Manning first developed swelling in the bursa in late February, which doctors treated by draining it and with anti-inflammatory agents.
Signs of infection appeared while Manning was in New Orleans in July, prompting surgery to remove the bursa sac and treatment with antibiotics to eliminate the infection, the team statement said.
The Indianapolis Star first reported Manning's staph infection Friday.
The Colts said the second surgery did not "materially" delay Manning's recovery.
"The second procedure was in no way, shape or form, related to the infection," the team said.
The Colts and Manning confirmed the second knee operation for the first time just last week.
Manning is the second high-profile quarterback to battle knee infections recently. Tom Brady of the New England Patriots reportedly had additional surgery to clear infections from his injured left knee. Brady was hurt in the season opener and is out for the year.