Ruben Dias will be out for four to six weeks because of a injury.
During their climb to the top of the table, Dias has missed just two games.
"Ruben is important for us, but he is not there." said City bossPep Guardiola on Friday.
Dias is expected to miss at least five matches, including the Manchester derby against United on Sunday.
"I don't love it, we need him a lot," said the coach.
I'm not going to cry. We only have two central defenders.
City have played one more game than their nearest rivals.
If they beat West Ham on Saturday, they will cut the gap to three points.
In September 2020, Dias joined City from Benfica.
He helped the club win the Carabao Cup and keep 26 clean sheets in 57 matches in the premier league.
Crystal Palace will be visiting City in the premier league on March 14.
After the international break, they play at Bournemouth in the sixth round of the FA Cup on 19 March and then at home to Burnley in the league on 2 April.
It is not known if Dias will be able to play in the home game with the Reds.