City travel to Old Trafford, looking to take another step towards the Premier League title, having defeated Tottenham 1-0 on Saturday.
Phil Foden’s early header separated the sides at the Etihad Stadium but the triumph was marred by an injury to De Bruyne, which forced the Belgian to be substituted.
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Guardiola admitted the extent of De Bruyne’s knock is as yet unknown but predicts the midfielder will not be in contention for the midweek trip to United.
“I don’t know,” he stated. “I didn’t speak with him or the doctors.
“It was something muscular, which is normal after injuries and three or four games of a lot of minutes with no preparation.
“Maybe he will miss the four games and the FA Cup Final. I don’t know how big the impact is.
“We will see tomorrow but I think for the next game, he will be out.”