Manuel Pellegrini has challenged his squad to fill the void left by Kevin De Bruyne's injury.
The inspirational De Bruyne faces up to 10 weeks on the sidelines after suffering knee and ankle ligament damage in Wednesday's Capital One Cup semi-final victory over Everton.
The 24-year-old had made a big impact after coming off the bench in that game, scoring and setting up another goal for Sergio Aguero.
This is typical of the impression he has made since his £54million club record signing from Wolfsburg last summer, having now scored 12 goals and assisted 12 others.
Pellegrini said: "It's a challenge for the squad and of course it's a challenge for the players that play where Kevin does. I think that Raheem (Sterling), Jesus (Navas), David (Silva) will have more responsibility knowing that Kevin is not here.
"It's impossible to have 25 Kevin De Bruynes in the squad, but I answer the same as when we couldn't play with Sergio Aguero.
"You have some players that are impossible to replace because they are top players - but we did it. We replaced Kun, we replaced David and we replaced Vincent Kompany. That is why we are involved in all the competitions and three points from the leaders of the Premier League.
"Now we have to replace Kevin. If you tell me we are going to replace him with any player: no, because he is a very important player, but as a team we must find a way to replace him."
City at least have Aguero getting back to something approaching his best form after his own injury problems. The Argentina striker missed 11 out of 14 games in the autumn because of hamstring and heel problems but has now scored six in his last five games.
Pellegrini said: "I never tried to find an excuse and complain about those things because they are part of the game.
"I am concerned not to have all the players together playing in the same moment and I think that Kevin was a very important assister for goals, but we made all the first part of the season without Kun and with Kevin.
"Now in the second part we must change it, now we are going to do it without Kevin but with Kun."
Pellegrini hopes De Bruyne can be back in action by the end of March and expects the player to deal with his setback positively.
He said: "He's not happy with what has happened but he will be optimistic, and it's very important to have his clear mind that he can return before if he works hard. I'm sure that he will make all his efforts to do it."
Pellegrini does not believe De Bruyne's injury is serious enough to risk de-registering him from City's Champions League squad.
City could make changes to their 25-man roster for the knockout stages of the competition - and the deadline to do so is next Tuesday - but Pellegrini hopes De Bruyne will be back for the latter rounds, if his side get there.
The alternative would have been to include highly-rated striker Kelechi Iheanacho, who missed out on selection for the group stages because City had already filled their quota.
Pellegrini said: "We hope Kevin will be ready at the end of March, so he will just miss the one round of 16. So I don't think we will take him out of the Champions League list."
Pellegrini has previously said City will continue to monitor Samir Nasri, who is recovering from thigh surgery, with regards to his Champions League eligibility until the deadline.