David Silva will miss the final Champions League Group F game with a hamstring problem picked up against Chelsea, and he joins Kevin De Bruyne, Danilo, Sergio Aguero, Benjamin Mendy and Claudio Bravo on the sidelines.
The boss says Aguero may be back in time to face Everton on Saturday, but admits Silva could be out for “a few weeks”.
“Silva not able, Kevin not able, Danilo not able, Sergio isn't ready," he said.
"[Silva will be out for] a few weeks. Last game he was substituted, not too big but he stops for a few weeks.
"Maybe he [Aguero] has a chance for the weekend."
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With City in the midst of a run of 14 games in 44 days, Guardiola would ideally have options available to him to rotate his side in the coming weeks.
And with progression to the last-16 already confirmed, many felt Wednesday’s game against Hoffenheim would provide an opportunity to do just that.
But Guardiola dismissed rotating his pack for the visit of the German side, saying he simply doesn’t have the players available to do so.
“We have 15 players available, so I can’t do it too much,” he said.
“We have 15 players tomorrow it’s a really tough game. We are in next stage which is important but we have to try and win every game, to finish first.
“Last-16 is always tough but in general the next Monday when there is a draw it’s a success we are there and the team we will face will be tough.
“They were incredible against Donetsk and they lost. It was incredible and fascinating to watch as a spectator.
"My admiration for Hoffenheim has increased. I knew about Julian Nagelsmann and his team but now I realise how tough tomorrow will be.”