Victory over Manchester United last weekend lifted Mark Hughes' side to 11th in the Premier League table, their highest position since Christmas.
However, Stoke remain just three points above the relegation zone and have only picked up five points on their travels this season, the joint-lowest tally in the division along with Hull City.
The last three meetings between Stoke and Southampton have ended level, with goalkeeper Asmir Begovic sensationally opening the scoring for Hughes' men in November’s 1-1 draw at the Britannia Stadium.
Southampton is not a happy hunting ground for Stoke, who have not won at the south-coast club since 1980.
Despite that record, Hughes is confident his team can build on their 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 said ahead of the trip.
"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 are hopeful that Marko Arnautovic and Jon Walters, who each limped off last weekend, 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.
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