Pep Guardiola has confirmed Ruben Dias will miss Sunday afternoon's Manchester derby.
Premier League leaders Manchester City will welcome Manchester United to the Etihad, knowing they can't afford to lose against their local rivals.
Guardiola's side are just six points ahead of title foes Liverpool having played a game more. Bragging rights, of course, are also at stake.
Dias is one of City's most important players, playing 25 of their 27 Premier League fixtures this season. He is the reigning Football Writers' Association (FWA) Player of the Year.
But the Portuguese defender is now expected to be out for between four to six weeks with a hamstring injury.
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Nathan Ake will also miss Sunday afternoon's game after suffering a knock in the 2-0 FA Cup victory against Peterborough United on Tuesday evening.
"Nathan and Ruben are not ready," confirmed Guardiola on Friday afternoon.
When pressed on how long Dias will be out for, the City boss said: "Muscular. Hamstring. Four to six weeks. It happens. In other seasons our best players have been out for months.
"I'd love him but he's not there, I will not cry. It is what it is. We have decent players available. We have 14-15 players.
"With these players we are going to fight and try to play good. Impossible to fight if you don't play good. We play with our people and hopefully our people support as they always do."
Although Guardiola will be without Dias and Ake, Zack Steffen is expected to make the bench after missing the last four games with a back injury.
United, meanwhile, are hoping to have Scott McTominay (illness) and Edinson Cavani (groin) available for selection, with the latter set to face a late fitness test.
City have a poor home record against United - winning just one of their last seven meetings at the Etihad - but Guardiola's side did win 2-0 at Old Trafford last November.
When asked about his team's preparations for the derby, Guardiola said: "It's a derby for our fans, we try to win the derby that helps us to win the league.
"Nothing changes. We know how good our opponent. You have to win most of your games. It's not for the pleasure to win, win this game, previous seasons we lost.
"I'd sign right now to lose Sunday and win the Premier League. It's not the Carabao Cup. It's a game, we fight with energy on the pitch.
"I can see the table from United, how many points behind us... I see they are so good.
"It [defeat to United] happened in the past, football must be played with emotion, otherwise would be boring. Have to control the emotions."
On why away teams perform better in the Manchester derby, Guardiola said: "We won more there than here. No specific reason.
"In all the games we were there, a better strength and quality from United. With Rashford, Sancho, unstoppable and quicker. We defend deeper and counter attack."
