France international star Nasri was carried from the field on a stretcher after being felled by Newcastle's Mapou Yanga-Mbiwa's 75th-minute challenge during City's 2-0 win at St James' Park on Sunday afternoon.
Pellegrini claimed the injury was "very serious" and believes he has suffered medial ligament damage, although a scan on Monday will reveal the full extent.
The City boss is now looking to bring in possible reinforcements to cope with the loss of the former Arsenal man who has been in impressive form in the club's march to the top of the Premier League.
Spain international Isco, who played under Pellegrini at Malaga, has been linked with a move to the Etihad Stadium.
The 21-year-old snubbed City to join the Spanish giants in the summer but he has struggled for first-team action under Carlo Ancelotti at the Bernabeu and might now fancy a move to the Premier League.
Isco would be cup-tied for City's Champions League games but would be a very useful acquisition for the upcoming glut of fixtures in the Premier League, FA Cup and League Cup.