Manchester City duo Oleksandr Zinchenko and Rodri are set to miss up to six weeks with injuries, adding to existing defensive concerns for manager Pep Guardiola.
Left-back Zinchenko has undergone minor surgery on a knee problem and midfielder Rodri, who has been deputising at centre-back, picked up a hamstring injury in midweek.
Both players look likely to miss the crucial trip to title rivals Liverpool on 10 November, as well as the visits of Aston Villa and Southampton.
Ukraine international Zinchenko posted a picture from his hospital bed on his Instagram account after surgery in Barcelona.
The 22-year-old has played seven of City’s nine Premier League matches so far this season and also helped Ukraine qualify for the 2020 European Championships.
“He had a contact with a knee. He felt something in the bone and has to stop,” Guardiola told a news conference before Saturday’s Premier League match with Villa.
“He had something to clean up the knee. It was not a big issue. Five or six weeks.”
Spain international Rodri had been deployed at centre-back against Crystal Palace last weekend and in Tuesday’s Champions League clash with Atalanta, before hobbling off in the first half.
“They told me after the [November] international break maybe he will be ready again,” Guardiola said.
City are already short of defensive cover with centre-back Aymeric Laporte sidelined until 2020.
John Stones made his comeback from injury with two substitute appearances over the past week, and Guardiola defended his decision to leave the England centre-back on the bench against Atalanta, in favour of playing converted midfielders Fernandinho and Rodri in the back line.
“It’s not about the first choice, it’s about being fit,” said Guardiola. “He has had many injuries. That’s why he couldn’t play.”