Sergio Aguero will miss City’s trip to champions Chelsea on Saturday following a car crash, though he is expected to return next month and could even line up against Stoke on October 14.
The news follows further bad updates on injuries to left-back Benjamin Mendy and captain Vincent Kompany.
It means Premier League leaders City visit title rivals Chelsea without key men, but Guardiola believes the club will need quality throughout the squad to achieve their long ambitions.
Looking ahead to the game at Stamford Bridge, Guardiola challenged his fringe players to step up. The 46-year-old said: “We have to overcome these situations. How we react is what I want to see.
“If people are saying we can’t do it now, we’ll never reach what we want in the next five or six years.”