Mark Hughes' side made an encouraging start to the new campaign, but have struggled to follow up back-to-back wins over Crystal Palace and West Ham in August.
An improved performance at Old Trafford in Stoke's last league outing went unrewarded as Manchester United came from behind to claim a 3-2 victory.
However, despite occupying 17th place in the table, Stoke have lost only once on home soil and go into this weekend’s game buoyed by qualification for the quarter-finals of the League Cup.
While the Britannia Stadium outfit needed extra-time and penalties to see off Birmingham City in a match that finished 4-4 after 120 minutes, Southampton were able to rest as their last-16 clash with Sunderland was postponed.
The south-coast side are unbeaten in seven across all competitions and sit fifth in the league with a tally of 18 points from nine games.
In addition, Mauricio Pochettino's men boast the best defensive record in the league having conceded just three in nine games.
Stoke have managed a paltry six top-flight goals thus far, although two of those did come last weekend and four different players – Oussama Assaidi, Peter Crouch, Marko Arnautovic and Kenwyne Jones - were on target in the club's midweek cup tie.
Southampton surrendered a 3-1 lead to draw 3-3 on their last visit to Stoke, Cameron Jerome - now on loan at Crystal Palace - grabbing a sensational injury-time equaliser.
Pochettino could be boosted by the return of Steven Davis and Pablo Daniel Osvaldo, who both face late fitness tests after missing the 2-0 victory over Fulham with knocks.
Stoke boss Hughes has no new injury doubts and is likely to recall Asmir Begovic, Geoff Cameron and Erik Pieters after the trio were rested at Birmingham.
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