The Argentine striker, whose last-gasp goal against Queens Park Rangers sealed the title for City in dramatic fashion back in May, was carried off on a stretcher after 13 minutes.
City's top scorer last season looked in severe pain after a tackle before getting to his feet and then dropping to the floor again but he later said he had not suffered a serious injury.
After City had come from behind to win, Aguero said on his Twitter account: "The studies I had done revealed there's no significant injury but it was a very tough hit to my knee.
"Tomorrow, the physicians will evaluate the time it will take for me to recover.
"I can't muster words to thank (you) for your concern and, with this much support, I'll probably get back up on my feet soon.
"And I want to congratulate my team mates for their effort in turning this game around."
Any long-term absence for Aguero would be particularly agonising for City having missed out on striker Robin van Persie, who opted to join Manchester United after leaving Arsenal.
"I think we need to wait two days for the scan," City manager Roberto Mancini told Sky Sports after the match.
But City's comeback in a thrilling victory over promoted Southampton proved they have goals throughout the team.
In scenes reminiscent of May's title triumph against QPR, Carlos Tevez, Edin Dzeko and Samir Nasri scored as City came back from 2-1 down to win late on but Mancini hopes this is the end of nerve-jangling finishes.
"I hope it is the last day like this. I remember the other very well. But it is important that we won this game because the first game when you start the season is always difficult," the Italian said.
"It's important we have this character but next time it is better we close the game before.
"I think today is only because it was the first game, we work together only for two weeks... we need to improve more our situation."