In addition there are big-money acquisitions David Silva, Mario Balotelli and Edin Dzeko at his disposal, while Aguero's fellow Argentina international Carlos Tevez remains with City despite expressing his desire to leave this summer.
"Silva, Tevez, Aguero, Dzeko, Balotelli - it is difficult," Mancini said.
"I think probably during the games there will be some moments when we can try to put all these players on the pitch.
"But it is difficult and we have to have a good balance for the team."
He added: "All these players are professionals and it is important that they are not happy when they don't play.
"If there is a player who is happy when he doesn't play, this is not good. They must be ready."