Wearing the captain’s armband on the night, De Bruyne had struggled to get into the game too much from a central attacking role.
He was trying to help City find a route back into the game early in the second half when he collided with Antonio Rudiger - the Chelsea centre-back getting a yellow card for the incident.
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However, the damage was more immediate and longer-lasting for City, as De Bruyne needed attention on the pitch from the City physios, before being deemed not fit enough to continue and being replaced by striker Gabriel Jesus.
In the first half, Chelsea had lost their own key man to injury, Thiago Silva going off with an apparent groin issue.
At the hour mark, Thomas Tuchel’s side remained ahead after Kai Havertz’s goal.