John Stones has been ruled out for a month with a muscle injury, Manchester City manager Pep Guardiola has confirmed.
City's defensive options had already been hit by Aymeric Laporte being ruled out for six months by a knee injury, while no replacement was signed for departed club captain Vincent Kompany.
That left Stones and Nicolas Otamendi as City's only senior centre-backs and the pair looked shaky last time out as the champions went down to their first Premier League defeat since January, losing 3-2 away to promoted Norwich City.
City will be further stretched for the upcoming period after Guardiola told reporters ahead of a Champions League trip to Shakhtar Donetsk that Stones was injured in training on Tuesday.
"A month, four or five weeks," Guardiola said when asked how long Stones would be out.
Guardiola previously indicated full-back Kyle Walker and defensive midfielder Fernandinho - an unused substitute against the Canaries - could be options in the heart of City's defence.
The City boss said he could also turn to teenage duo Eric Garcia and Taylor Harwood-Bellis to address the growing injury crisis at the back.
"[It is a] Big challenge. For me as a manager, it's an incredible challenge: just one central defender in Nico," he added.
"But I believe a lot. People don't know the spirit and resolve to solve this problem. The players are going to come back with Fernandinho, Garcia, Harwood-Bellis.
"It's happened, but what we are not going to do is complain. If they are not able, they are not able. We have to have 11 players on the pitch, and I like it, finding a solution.
"Football is not about how you deal with the good things but how you deal with the problems. Nobody gave us anything when we win the last seven titles and we are going to do the same [fight for titles]. I'm ready for the challenge, I like it. We will deal with the situation."
Fernandinho is set to deputise at centre-back against Shakhtar although the Brazil international has yet to feature this season.
"He arrived late, and he's a player who's 34 and needs minutes and rhythm," Guardiola said.
"So, he trained the last after the international break really well. The family is back with him, which is important for him because the first period he was alone.
"With his experience and personality, he can play that position because sometimes he played there last season, and now with Eric and Taylor we will use him in that position with Nico."
Stones will likely miss Premier League games against Watford, Everton and Wolves at least as well as an EFL Cup trip to Preston North End and a Champions League home game against Dinamo Zagreb.
City will also be without Phil Foden against Shakhtar, with Guardiola confirming: "He has a virus, a problem with the stomach. He's not able [to play] this game or I think the next."