The Saints were rested midweek as their Capital One Cup tie with Sunderland was postponed, while the Potters needed extra time and penalties to get past Birmingham City.
Mark Hughes' side made an encouraging start to the campaign but has 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, the Potters have lost only once on home soil and go into this game buoyed by qualification for the quarterfinals of the Capital One Cup, eventually seeing off Birmingham City - though they needed extra time and penalties, the game having finished 4-4 after 120 minutes.
Southampton, by contrast, was able to rest as their last-16 clash with Sunderland was postponed. The south-coast side is unbeaten in seven across all competitions and sits 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 has scraped a paltry six top-flight goals thus far, although two of those did come in their last game and four different players – Oussama Assaidi, Peter Crouch, Marko Arnautovic and Kenwyne Jones - were on target against Birmingham.
In its last visit to Stoke, Southampton surrendered a 3-1 lead to draw 3-3 at the Britannia Stadium, with Cameron Jerome - now on loan at Crystal Palace - grabbing a sensational injury-time equalizer.
Pochettino could be boosted by the return of Steven Davis and Dani Osvaldo, who both face late fitness tests after missing the 2-0 victory over Fulham with knocks.
Hughes, meanwhile, has no new injury doubts and is likely to recall Asmir Begovic, Geoff Cameron and Erik Pieters after the players were rested at St Andrews.