The Serbia centre-half was carried off on a stretcher after suffering an ankle injury in last month's Barclays Asia Trophy final against Sunderland in Hong Kong.
An article on the club's website has now revealed the 20-year-old could be sidelined for four to six weeks.
Nastasic made a big impression at the Etihad Stadium following his move from Fiorentina last summer but his absence could allow Joleon Lescott the chance to revive his title-winning central defensive partnership with Vincent Kompany.
Meanwhile, striker Sergio Aguero is poised to return to full training before the end of the week.
Aguero is yet to feature during City's pre-season programme because of a knee injury.
City face Arsenal in a friendly in Helsinki on Saturday before beginning their Premier League campaign against Newcastle on August 19.