The Argentina striker went down after a tackle after just eight minutes and was stretchered off after clutching his knee.
Now the Blues will have to wait until early next week to discover the extent of the problem – and Mancini is keeping his fingers crossed for good news.
“I am worried about Sergio because anything around the knee is dangerous and this injury was so strange. We will have to wait, but we are not sure exactly what the problem is at this point,” said the City boss.
“We will know more after he has had a scan. Until then, we must wait.”
Mancini added he was relieved with the victory over Southampton, but the somewhat shaky victory down to the fact it was the first game of the campaign.
“We must defend better than we did but we’ve only been back together as a team for two weeks and we will improve.
The first game of a new season is never easy so I am happy we have ended with a victory today
...Mancini
The City boss also admitted there is a chance Adam Johnson may be allowed to leave before the transfer window, saying: “Adam is a very good young player who wants to play football. I understand this so if we can find a solution for him in the next ten days or so, we will.
“It is difficult for him and I understand his situation and are talking to him about it at the moment, but if he stays with us, that is fine, too. We will have to see what happens.”
Saints boss Nigel Adkins praised his team’s display and believes his players will take a lot of heart out of their narrow defeat to City.
“We’ve come away from home to take on the champions and we tried to find a way we could win this game,” he said. “That’s what we tried to do and our defence have just faced the best forward line they’ve ever come up against and they didn’t do too badly.
“City conceded only 12 goals at home last season and we’ve just scored twice. They only dropped two points at home and we pushed them hard today, so our lads can take a lot from this game. We’ve had back-to-back promotions so we’re used to winning games but we know it will be tough this season.”
Adkins admitted he hadn’t seen the tackle that resulted in Aguero’s injury but hopes the City striker makes a speedy recovery.
