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The City captain has not completed a full training session with the rest of the first-team squad in a month and he will not be considered for the crucial Premier League game at Stamford Bridge.
He has been called up to the Belgian national squad for their upcoming matches with Bosnia and Herzegovina and Cyprus – but Guardiola says he will not play for the Red Devils.
"No way [will Kompany be fit to play against Chelsea],” he said.
“He didn’t make one training session with us since one month ago, the Gibraltar game.
“I spoke to Roberto Martinez [Belgium manager]. He told me he will go there to meet with the Belgium doctors but he is coming back.
"Of course he cannot play with Belgium."
Guardiola will also be without Benjamin Mendy after he suffered a knee injury in the win over Crystal Palace last weekend.
Guardiola says he expects the Frenchman to be out until April.
Mendy, signed from Monaco in the summer, is currently in Barcelona and will undergo an operation later today to cure the problem.
Mendy was successfully operated on this afternoon in Barcelona by Dr [Ramon] Cugat but will be out for an extended period of time.
Aguero was visiting the Dutch capital on his day off when the incident happened, and Guardiola was relieved his striker came away without too much damage.
“Sergio, as you know, has had an accident in Amsterdam and he will be back this afternoon,” he said.
“I don't know, I am not a doctor, I don't know exactly what he has. It was an accident. Fortunately, he will come back and recover as soon as possible.
“It was his day off, I'm not the police. I would prefer to be with Mendy, with Kompany and with Sergio Aguero [but] we will play with eleven.
"The first impression we have is he has broken the rib. Exactly how many days he will have off, I don't know right now."
The City forward was in Holland on his day off and has sustained injuries.
Ex-Chelsea man Graeme Le Saux has been explaining who his former side need to watch out for.
The latest on Benjamin Mendy's injury setback..