The Championship promotion-hopefuls have revealed that McCann suffered a multiple fracture of his right knee cap in a collision with City defender Micah Richards during Sunday's shock 2-1 win at the Etihad Stadium.
McCann has become a key player since his move from Lancashire rivals Burnley in June and his injury is another major setback for Wigan, after fellow midfielder Ben Watson suffered a double leg fracture last month.
Wigan are in the hunt for an immediate return to the Premier League and also face Arsenal in the semi-final of the FA Cup as they attempt to retain the famous trophy.
McCann's injury is being assessed by specialists, who will then make a decision on whether the Irishman requires surgery.
Wigan manager Uwe Rosler was left to rue losing another influential player at a key stage of the season.
"It's a massive blow for us and for Chris, especially coming so soon after the injury to Ben Watson," Rosler told the club's official website.
"We will do everything we can to make sure Chris gets back to action as quickly as possible and in the best physical condition he can be."
