Stoke captain Ryan Shawcross is to undergo back surgery and will be out for at least two months, the club have announced.
Shawcross, 27, is to have the operation next week having suffered a recurrence of the back problem that troubled him last season.
A statement on the Potters' official website on Thursday said: "The club had hoped surgery would not be necessary and that the summer break would provide a solution.
"That initially appeared to be the case, but the harder Shawcross pushed himself in preseason the more discomfort he found himself in, leaving no alternative but for him to undergo the operation."
The news is a significant blow for Stoke three days before their 2015-16 Premier League campaign kicks off with a home clash against Liverpool.
Shawcross has consistently been a key figure during the Potters' seven-year stint as a top-flight club following their promotion in 2008.
He initially joined them on loan from Manchester United in the summer of 2007, signed on a permanent deal in January 2008 and has made over 300 appearances for the Staffordshire outfit in total.
The loss of Shawcross could see Stoke boss Mark Hughes move again in the transfer market having already made eight signings this summer.
Hughes has the likes of Marc Wilson, Marc Muniesa and Philipp Wollscheid as options already at his disposal for providing cover.
And Stoke goalkeeper Jack Butland told the BBC of once-capped England international Shawcross: "To lose him is a big loss, but we've got players capable of filling the void.
"The likes of Geoff Cameron, Marc, Philipp and Muni are top-class centre-halves and would be brilliant replacements."