Glenn Whelan could be out of action for six weeks, meaning the Stoke City defensive midfielder could miss out on two matches against the Saints, as well as West Ham United, Tottenham Hotspur and Burnley.
Glenn Whelan, of Stoke City and the Republic of Ireland, has suffered a "slight fracture" in his leg after being kicked whilst on international duty and will subsequently be out of action for the foreseeable future.
The defensive midfielder, who has returned 18 tackles and 17 clearances from seven outings in the Premier League thus far this season, will therefore not be available for selection for the matches against Southampton in the league and League Cup and also West Ham United, Tottenham Hotspur and Burnley.
“He got a kick on the outside of his leg, and there is a slight fracture there," confirmed Potters boss Mark Hughes.
"He's not been put into a plaster cast. We're going to try and manage it without that because Glenn feels he'll get back sooner.
"But the likelihood is he's going to be out for four to six weeks I'd imagine, which is a blow for Glenn obviously because he is a big part of what we're doing, and we'll miss him.
"He's been playing really well of late, but we'll get him back as soon as we can.
"As for Ireland, knowing Glenn he'll try and make himself available, but my feeling is the game will be too soon for him.
"You have to let nature take it course. With fractures you have to give them enough time to heal."
Stoke will also be hampered by the back injury sustained by Phil Bardsley, who may also be a doubt for the Saints clash at St Mary's this weekend.
He told the club's official website: “Phil locked up a little bit during the game on Sunday, so he is a doubt ahead of the game.
“He hasn’t trained today, but we will see how he is again tomorrow and hopefully get him back into the group then. We will have to wait and see how he is, but at the moment he is rated as doubtful for the game.”