De Bruyne suffered a knock to the calf during the first half of City’s 1-1 draw with Southampton at the weekend and won’t feature at Old Trafford.
However, his injury isn’t thought to be serious and he could be back in contention for the weekend’s trip to West Brom.
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Pablo Zabaleta is a doubt having failed to fully recover from his recent foot problem – and with Bacary Sagna also on the treatment table, Guardiola may be struggling for a senior right-back once again.
“Kevin, no way, he cannot play,” Guardiola confirmed. “Hopefully West Brom but he is doubt even for the weekend.
“Pablo I think cannot play against United.”
Captain Vincent Kompany, who made his first league start since April on Sunday against Southampton, hasn’t suffered any adverse reaction to his recent groin problem – but Guardiola wants to see how he reacts to this afternoon’s training session before declaring him fit for the game with United.
“Vincent I think he can but I don’t know today,” he said. “I need to see training and regeneration [before making a decision].”