The German suffered a calf injury in training on Monday that the Potters fear could rule him out for a number of weeks.
Full-back Phil Bardsley is available despite continuing to struggle with soreness in his back but midfielder Glenn Whelan remains on the sidelines with a fractured leg.
Stoke have the rare chance to take immediate revenge for Saturday's result between the two teams - a 1-0 Premier League loss - and this time the game will be played at the Britannia Stadium, where the Potters will look to make it three victories in a row.
Southampton's win took them up to second in the Premier League table, only four points off leaders Chelsea, and assistant boss Mark Bowen is looking for his side to put in a better showing.
"We've looked back at it with the players and we probably didn't play the game we wanted to play, certainly in the first half," he said.
"There was a little bit of looking at their last game (an 8-0 win over Sunderland) maybe and too much respect for them.
"In terms of trying to get on the ball and play, I didn't think we approached it right
In the second half I thought we were well in the game, without creating any clear-cut chances.
"It's strange (playing them again) because you're always wondering whether they're going to set up the same
(Saints manager) Ronald (Koeman) has gone quite strong in the cup games the way we have so we don't expect too many changes.
"We've got the added bonus of our fans behind us, and we are a different side at home so that will hopefully play into our favour.
"We don't underestimate the problems they can cause but we've got a few things up our sleeve that we can throw at them as well."
Southampton manager Ronald Koeman expects Stoke to once again provide a tough challenge.
A Sadio Mane first-half strike proved the difference between the two teams at St Mary's on Saturday.
That only told half the story as although Saints dominated the opening 45 minutes, they were given some scares towards the end of the encounter before holding on for all three points to move up to second in the league.
"I don't think (Stoke will play that differently) - in football you know everything of each other and there are no surprises," said Koeman in quotes reported by the Daily Echo.
"We have our way of playing
The way of playing of Stoke is different
Now we know it's a tough opponent and we have to work hard.
"In the first half on Saturday we showed our qualities and we were the best team on the pitch.
"But if you don't score the second one and you create a lot of opportunities then you know until the last second it is 1-0 and it is very difficult."
While he is keen to progress in the cup, Koeman may opt to rest some of his key players, with his side flying high in the league, but insists he will not make wholesale changes.
"We don't have that quality to change eight or nine positions because the group is not like the big teams in England," he added
"I don't like that because I like rotation, but not to change everybody."
Source : PA
Source: PA