Centre-back Stones faces six weeks out with the hamstring injury sustained in Saturday's win at Leicester.
The return of captain Vincent Kompany at the weekend after his own lay-off is timely but, given the Belgian's patchy fitness record, the Premier League leaders do appear short of defensive cover.
Nicolas Otamendi will return from suspension but the only other specialist options are the much-maligned Eliaquim Mangala and largely untried youngster Tosin Adarabioyo.
"We don't have a big squad," said City boss Guardiola ahead of Tuesday's Champions League clash with Feyenoord. "It is a big pity we lost a month and a half of Vincent Kompany in the national team and now John Stones. To win the titles we need all the squad, especially important players like John and Vinny.
"On the other side, we have an opportunity. We have to play 12 games in a short space of time with only three central defenders. One of them is a risk, in Vincent only just back.
"It is not easy but I want to see how we react. Always when you are champions you have to handle the big situations, the tough situations.
"When everyone is ready and comfortable, that is not when you get credit. We are going to see how we react in the most important moment of the season. Until Watford, on January 2, it is about how we react."
Mangala, who spent last season on loan at Valencia, looked set to leave the club in the summer but City's failure to sign Jonny Evans from West Brom earned him a reprieve. He replaced Stones following his injury at the King Power Stadium.
The 26-year-old said: "Football is like this. You have to be ready to take the opportunity. We need more than 11 players. Every player has to be ready to play."
As well as weighing up the permutations, Guardiola admits deciding which of his lethal strikers, Sergio Aguero or Gabriel Jesus, should play is an even harder call.
He said: "Now it is the toughest decision because both with their different qualities and they deserve to play. They have a lot of games and they have to be ready and prepare well."
Guardiola added that he has not played both together recently, as he did earlier in the season, because injury to left-back Benjamin Mendy has increased reliance on winger Leroy Sane.
City have already secured a place in the Champions League last 16, so the pressure is off for Feyenoord's visit to the Etihad Stadium.
But Guardiola said: "The first step we have done, we are already qualified, but I prepare the same way as always (on Tuesday) and that's to win the game."
Related links
