Pep Guardiola has confirmed Kevin De Bruyne, Kyle Walker, Jack Grealish and Jeremy Doku all remain unavailable for Saturday's home Premier League game against Southampton.
Guardiola, who named only 15 outfield players in his squad for this week's Champions League win against Sparta Prague, also admitted he had no idea when De Bruyne would return to contention.
When asked if De Bruyne and Walker were available, Guardiola said: "No, not yet."
And when pressed on whether De Bruyne's extended absence due to a thigh injury was a concern, Guardiola added: "Yes of course. I'd prefer to have all the squad (fit) with the amount of games, but it is what it is.
"Hopefully he can come back soon. I don't know (when) yet. I would like to tell you, but I don't know."
Playmaker De Bruyne has been out since mid-September, while right-back Walker sustained a knee injury while on England duty earlier this month.
Doku and fellow winger Grealish were added to City's injured list earlier this week and missed Wednesday night's 5-0 triumph over Sparta.
When asked if either of those two would be back, Guardiola replied pointedly "no" and refused to embellish further on his latest injury woes.
On a positive note, Guardiola said he had not been worried about Phil Foden after the midfielder showed encouraging signs of a return to form in midweek with City's opening goal.
Foden admitted he had suffered from 'burn-out' after last season's exploits with City and England earned him the Premier League player of the year award.
Guardiola added: "I'm not concerned at all about how far it is (a return to top form) because I know when he is fine, he will get it. He's a natural talent, he will get it.
"The first goal against Sparta Prague, finally with his incredible talent, he solved the game for himself.
"But in a career when you have many, many years, and Phil already has many years, you have these bumps, ups and downs a little bit.
"They are human beings. Be patient. Let them feel that this type of player in these types of moments, that we are there and everything is going well.
"Sooner or later. I'm happy to hear that he feels good because in the end it depends on himself."
City are big favourites to secure a seventh victory in nine league games on Saturday against winless Southampton, who are second bottom in the table.
Saints boss Russell Martin, whose future has come under the spotlight, has insisted he will not be changing his football methodology after his side's poor start and Guardiola was in full support.
Guardiola added: "He will have success. When this happens, you always have success sooner or later. I'm not talking about whether it's four at the back or five at the back, that's not the point.
"But if you start to change your thoughts for the results, the players will notice. They will know you're not a big believer. When this happens, sooner or later bad results are coming."