Mark Hughes has confirmed that Bruno Martins Indi is facing a possible eight weeks on the sidelines through injury, while Stoke City will also be without Jese Rodriguez for Saturday's (9 December) Premier League trip to Tottenham Hotspur.
Former season-long loanee Martins Indi, who has made 10 further appearances for Stoke since completing a permanent £7m ($9.4m) move from FC Porto in August, had to be stretchered off during the second half of the 2-1 comeback victory over Swansea City last weekend after being hurt during an innocuous challenge from Wilfried Bony.
Hughes initially expressed concern that the centre-back would miss "three to four weeks minimum" as the result of a groin problem, although it now appears that the top-flight's second-most porous defence will once again be missing a key starter for up to two months.
"Bruno, as we feared unfortunately, is likely to be out for quite some time," the manager told reporters during his pre-Tottenham press conference on Thursday afternoon.
"The worst-case scenario is eight weeks, but we hope he will be back before then.
"He has really damaged the groin area. We sensed that on the day, he was in a lot of pain. He has started his treatment already, but it will be a long process."
Paris Saint-Germain loanee Jese made just two substitute appearances in November and will be unavailable to face Tottenham having travelled back to Gran Canaria, where his infant son Nyan, who was born four months premature, is still in hospital.
"At the moment there is an on-going issue with his child's health, and he won't be available this weekend," Hughes said. "He has had to go back home because of that, and that is worrying of course. We all send our best wishes to him and his family.
"The plan was to utilise him more over this period, but at the moment we aren't quite sure when Jese will be back. He, along with Saido [Berahinho] and Charlie Adam, are all in my thoughts."
Hughes also revealed that Jese had been internally disciplined by the club after leaving the bench and walking to the tunnel after it became clear that he was not going to be introduced against Swansea.
While Martins Indi, Jese and long-term absentee Stephen Ireland are all unavailable to face Tottenham, versatile defender Geoff Cameron is in contention for Stoke's first visit to Wembley Stadium since their 2011 FA Cup final loss to Manchester City.
The United States international has been carefully managed after suffering a concussion in training, last featuring in the home defeat by Bournemouth on 21 October, but is now ready to feature once more.
On his return, Hughes added: "Geoff Cameron has had a full week of training and he is available. We have been cautious with him, you have to manage head injuries carefully. There is a lot of discussion surrounding concussion and long-term affects of it, so we have adhered to the protocol.
"Geoff has to be comfortable in his own mind too, and we have allowed him the flexibility to do that. We haven't pushed him, we have let the injury run its course and hopefully he is over it now."