The Saints are looking to make it back-to-back wins after their defeat of Middlesbrough at home on Sunday, which would continue their perfect response, at least as far as results are concerned, to the lifeless, lethargic and laboured draw with Hapoel Be'er-Sheva last Thursday, which sent them bowing out of the Europa League with a whimper.
In Mark Hughes' Stoke team, Southampton face the side that is perhaps the most similar to them in the Premier League, if the table is anything to go by.
Improving the mood
After Southampton somehow fluffed their lines in Europe and failed to qualify for the knockout stages, the morale around the entire club was very low. Panic set it, the blame game began and the sheer frustration at failing to deliver in the biggest game of the season was evident from everyone on the South Coast.
Despite the Saints fans, staff, and players alike all yet to get over the intense disappointment of their tame display last Thursday, the response on the pitch has been positive at the very least. Although far from a classic, Southampton returned to winning ways three days later, seeing of Middlesbrough at home.
With the pain eased ever so slightly by this victory, Claude Puel's men now face Stoke away from home, knowing that a good performance and the three points is a necessity to ensure the gloomy air continues to be lifted above St Mary's.
Nothing between them
On paper, Southampton and Stoke are the definition of mediocrity at the moment in the Premier League. Occupying 10th and 11th, the two middle positions, respectively in the table, there seems to be very little to choose between the teams.
Current form too, suggests that this will be in an even encounter, with both sides taking seven points from their last 5 games.
However, despite losing their last game at Arsenal, it is surely Stoke who come into this game the narrow favourites. They were by no means outplayed in the defeat at The Emirates, and have only lost twice in their last ten matches. Southampton meanwhile, have not won away from home since late September.
Nevertheless, with both teams seeking vital points to pull away from the chasing pack below and cement their place in the top half, it looks set to be a tight and intriguing clash.
Both Ryan Shawcross and Jonathan Walters could return for Stoke after spells on the side-lines.
However, Marc Muniesa could miss out for the hosts with a knee injury, and Glen Johnson is doubtful with an eye infection.
For the visitors, the absence of top scorer Charlie Austin to a dislocated shoulder will be a big blow.
Southampton will still be without Matt Targett and Alex McCarthy, who are nursing hamstring problems.
Southampton are the joint second lowest scorers in the division. While Stoke haven't scored after half-time in their last five Premier League matches.
Southampton are yet to win from a losing position this season but Stoke lost from a winning position for the first time this season in their loss to Arsenal.
There's history between them
Only Stoke striker Peter Crouch has played for both sides out of the current squads.
It was two away wins when the sides met in the league last season, with Stoke triumphing 1-0 at St Mary's, before Southampton got their revenge with a 2-1 victory at the Britannia.
The clubs have met eight times in the Premier League era, with each side winning twice.