Aguero, who has scored six times in three matches for Manchester City this season, will not take part in this weekend's match as he starts the three-game suspension that he incurred for an elbow on West Ham United's Winston Reid before the international break.
Mourinho, however, has claimed that he would be able to prepare his team tactically for a match that involved Aguero and now there is uncertainty who Pep Guardiola will select as the Argentine's replacement.
"When Aguero is available, we know he plays. We know their formation and nobody has doubts when a player like him is ready, he plays," Mourinho told reporters. "He could decide to play with [Kelechi] Iheanacho or [Raheem] Sterling. He could decide to play with [David] Silva as a fake number nine between the lines. It is clear that they have many options.
"That for us, in the preparation of the game, makes us have to go step-by-step with every situation because we are trying to reduce the unpredictability of the game. To try to do this now is more difficult."
Aguero has scored 142 times in 211 appearances for Man City since arriving from Atletico Madrid in 2011.