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De Bruyne hasn't played since being forced off with a hamstring problem at Bournemouth a fortnight ago, a game that also saw Stones pick up a groin injury, while Kompany has suffered a setback from the muscle issue that saw him miss seven weeks at the turn of the year.
Benjamin Mendy and Fernandinho are also out.
Guardiola admits injuries mean he will not be able to rotate his side but says his focus is on getting through to the semi-finals of the FA Cup.
"We will have to make changes," he said. "Stones on bench, not ready to play. He is still recovering.
"Vinny and Kevin not fit. We don’t have too many options.
"Tomorrow is a quarter final, that is the most important thing by far, to reach the semis."
Earlier today, City were drawn against Tottenham in the quarter-final of the Champions League, meaning we will face Mauricio Pochettino’s side three times in 11 days during April.
Guardiola says he has the utmost respect for Spurs, a team he feels he knows well having watched them closely during his time in England, and admits the reduced travel time will help his squad during the run in.
But he insists he isn't looking too far ahead.
"It’s the draw, it’s what it is," he said.
"When you have four Premier League teams in the draw you have a good chance to get one of them. It was Tottenham. I know quite well the quality of this team.
"Now Swansea, and we take a break for those who don’t go to international teams. Of course, going to London is closer than Catalunya, or other countries.
"The draw is what it is. Never in my life do I think too much about these situations.
"What I want is people to come back from international break fit and ready for the final two months. That’s all I am concerned about.
"Tottenham, huge respect of course. I know them well, the different systems they use. Experience in all departments. If you talk about any other team in Champions League, it would be the same.
"You cannot control the draw. The draw decides."
Ahead of our meeting with Spurs we have put together a guide to our familiar opponents...
Dates and times for the Champions League quarter-final have been confirmed by UEFA
Details of our Champions League quarter-final draw...