Stoke defender Marc Muniesa is out for up to six weeks with a torn hamstring.
The 22-year-old suffered the injury in Stoke's 4-1 FA Cup fifth-round defeat by Championship side Blackburn.
"We feared it was a really bad one. He had a scan and they've come back saying it's four to six weeks," assistant boss Mark Bowen told BBC Radio Stoke.
It leaves Stoke short of cover for their next game against Aston Villa with Ryan Shawcross also injured and Robert Huth on loan at Leicester.
"Ryan's had this back problem that he's had in the past and it's reared its ugly head again," said Bowen.
"He's gone in yesterday to see a specialist for some more injections.
"We're hoping it hit the right spot and, if so, over the next 48 hours it should progress significantly, but certainly not to put him in the frame for Saturday."
Former Barcelona defender Muniesa, who joined Stoke in 2013, has made 19 appearances this season.
"Over the course of the last two months you could argue he's been probably our best defender and showed a lot of maturity," said Bowen
"He's almost nailed down that left-hand side centre-half spot as his own."
Marc Wilson may be able take Muniesa's spot in the squad as Bowen expects him to start training on Thursday following a knee injury, and left-back Erik Pieters and midfielder Stephen Ireland could also be in contention against Villa.
And manager Mark Hughes is hopeful that forwards Jonathan Walters and Peter Crouch may be fit despite seeing specialists on Monday.
"They both went for injections yesterday that hopefully will settle them down," added Bowen. "They'll hopefully be able to train Thursday with a view to being able to play."