Mark Hughes's men, who sit 11th in the Premier League, are looking to build on last Saturday's victory over Manchester United but have not won away against the Saints since 1980.
Victory over Manchester United lifted Mark Hughes's side to 11th in the Premier League table, their highest position since Christmas, but the Potters remain just three points above the relegation zone and have only picked up five points on the road this season, the joint-lowest tally in the division, along with Hull City.
The last three meetings between Stoke and the Saints have ended level, with goalkeeper Asmir Begovic opening the scoring for Hughes's men in November's 1-1 draw at the Britannia Stadium.
Southampton is not a happy hunting ground for the Potters, who have not won away at the south-coast club since 1980. Despite that record, Hughes is confident that his team can build on its win over United and pull further clear of the bottom three.
"We have all been in good spirits and the atmosphere around the place is really good at the moment," he told reporters. "We feel we have the capacity within the squad to embark upon a good run of results. Of course, we would have liked to have done that already but, for one reason or another, we haven't been able to string together a series of good results. Hopefully we can do that now.
"We have to be nice and solid at Southampton because they are a very high-tempo team with good technical players. We need to have a good base to build upon and hopefully we will be able to keep them out and then look to cause the damage at the other end of the pitch. The key is getting that first goal and that is what we will be hoping to do on Saturday."
Southampton, unbeaten in six games across all competitions, will be without young striker Sam Gallagher (family bereavement). Victor Wanyama (knock) and Calum Chambers (dead leg) could feature, while Gaston Ramirez and Dejan Lovren (both ankle) are making good progress.
Stoke is hopeful that Marko Arnautovic and Jon Walters, who each limped off against the Red Devils, will be fit to retain their places.
Steven N'Zonzi is available again after serving a suspension, while both Andy Wilkinson and Matthew Etherington have returned to training following injuries, but Marc Wilson is doubtful with a chest infection.