Aguero's last appearance at Eastlands ended in memorable circumstances as he hit the stoppage-time winner against QPR that clinched City's first English title for 44 years.
But the 24-year-old lasted just eight minutes of his side's opening match of the Premier League season before being stretchered off following a challenge from Southampton defender Nathaniel Clyne.
Aguero received treatment for several minutes after collapsing to the turf in agony as he tried to continue playing.
Now Mancini has confirmed the striker will have to go for a scan that will determine how long he will be out of action.
"At the moment we don't know (how long Aguero will be out). We need to wait for the scan in two days," Mancini said.
Aguero, signed from Atletico Madrid for ?38 million last year, played a key role in City's title triumph, scoring 23 Premier League goals, and it would be a major blow for Mancini if he is ruled out for a long period.
Mancini was already frustrated by City's failure to sign Robin van Persie, who joined Manchester United from Arsenal last week, and Aguero's injury may prompt him to force his club to return to the transfer market.
Source: AFP
Source: AFP