The Latics midfielder sustained a blow during the FA Cup clash against Manuel Pellegrini's side and may require surgery
The 26-year-old sustained a multiple fracture of his right knee cap in a collision with City defender Micah Richards during the 2-1 FA Cup win at the Etihad Stadium.
McCann's injury may require surgery and Latics boss Uwe Rosler said that it was a "massive blow" to lose the midfielder.
"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."
McCann has become an important player since his move from Lancashire rivals Burnley in June and his injury is another setback for Wigan, after fellow midfielder Ben Watson suffered a double leg fracture last month.
Meanwhile, Eunan O'Kane has signed a new three-and-a-half year contract with Championship side Bournemouth.
The deal means that the former Republic of Ireland Under-21 international has committed to the club until the summer of 2017.
"I'm over the moon with it," O'Kane told the club's official website. "I'm here for the foreseeable future, there was never any doubt in my mind that I would sign."