The Portuguese centre-back and key man in City's defence will miss the Manchester derby on Sunday with a hamstring injury, that could also see him be ruled out for the huge clash against Liverpool on April 10.
Dias sustained the injury in the club's fifth round FA Cup victory away to Peterborough on Tuesday, in which he was taken off at half-time.
He will be out for 'four to six weeks', the manager confirmed.
Speaking in his pre-match press conference ahead of the match, the Guardiola also confirmed that Nathan Ake will not feature at the Etihad.
"It happens during a season," Guardiola said.
"One of our best players, Kevin [De Bruyne], was out for eight or nine months previously.
"I'm not going to cry. We have two central defenders [John Stones and Aymeric Laporte] but it is what it is.
"People say we were lucky with Covid but we have 15, 16 players in the last months. We will fight."
With Liverpool set to take on West Ham on Saturday, Jurgen Klopp's side can close the gap to three points at the top of the table, with a game still in hand.
City can re-establish their six point gap, for now at least, if they are able to secure the league double over Manchester United on Sunday, but will have to do it without one of their star players.