Graziano Pelle`s brace dealt Stoke`s Europa League hopes a real blow.
The Italian striker ended his 12 game baron run in front of goal with a neat header and calm low finish.
Marko Arnautovic scored just after the break to give Stoke a sniff but the Staffordshire outfit failed to capitalise on their breakthrough.
Saido Mane was given his marching orders late on after a clash with Erik Pieters.
The victory means that Southampton move above Stoke into 7th in the league table.
Southampton took the lead early on when Pelle managed to find himself free in the penalty area and flick the ball past Jack Butand.
Ryan Shawcross returned to the Stoke line-up following a back injury, but Stoke looked frail at the back as Graziano Pelle was able to create space and doubled his and Southampton`s tally.
Jack Butland should have done a lot better as the ball was hit straight at the England international stopper.
The embarrassment for Butland was enhanced as it was in front of his England goalkeeping rival Fraser Forster.
Stoke struggled to cope with Southampton`s counter attacking style, with Shane Long and Pelle dominating and bullying Wollscheid and Shawcross in the heart of the Stoke defence.
The Potters really struggled to create anything of note in the first half and the half-time whistle was very welcoming to the fans, players and management alike.
Mark Hughes team came out in the second half with a little more fight and managed to drag their selves back into the game following some great work from Ibrahim Afellay on the right wing, who managed to find Arnautovic who produced a clever finish to give Stoke hope.
There was a real expectation that Stoke would now kick on and drag their selves back into the game, but other than another Arnautovic opening which was well saved by Forster, Stoke failed to create any real clear cut chances.
Southampton looked the more likely to add their tally, and were denied a stone wall penalty when Dusan Tadic was brought down in the box but Lee Mason waved away appeals.
Substitute James Ward-Prowse nearly put the game to bed but his free kick was well saved by Jack Butland, who managed to push his effort onto the crossbar.
Stoke`s downfall was mainly down to the fact that they could not keep the ball away from the dominating Virgil van Dijk, who produced a dominating display at the heart of the Saints defence.
Ronald Koeman`s side were on the end of another dubious refereeing decision as Saido Mane was given his marching orders after he clashed with full back Pieters.
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