The Argentine striker remains in self-isolation after being deemed a close contact of an individual who returned a positive test for Covid-19.
Record scorer Aguero – who has made only nine appearances and netted two goals in total during an injury-plagued campaign to date – missed the recent wins over Crystal Palace, Brighton and Birmingham and will not return at the Etihad Stadium on Wednesday evening.
Gabriel Jesus should lead the line once again for in-form City against Villa, but Aymeric Laporte remains sidelined along with Aguero.
The French centre-back is back in training after injury, though looks set to return in Saturday’s FA Cup fourth-round tie against League Two outfit Cheltenham Town.
Fellow defenders Nathan Ake and Eric Garcia are still out, with John Stones and impressive summer signing Ruben Dias set to continue their backline partnership.
“Sergio is not ready for tomorrow. He is still isolating,” City boss Pep Guardiola said at his pre-match press conference on Tuesday.
“I don’t know (for how long.) Aymeric is at the last step. He is not ready for tomorrow, but he is training with us. Yesterday was the first one, today was the second.
“Hopefully (he will be available for the weekend). That would be good news. We need him. We cannot play with just Stones and Ruben. We need Nathan, Eric. We need Laporte.”
Predicted Man City XI to face Aston Villa (4-3-3): Ederson; Cancelo, Stones, Ruben Dias, Zinchenko; De Bruyne, Rodri, Gundogan; Mahrez, Jesus, Sterling