Despite reaching the League Cup final and another solid league campaign, there is still question marks over the future of Saints boss Claude Puel - who only replaced Ronald Koeman last summer.
One of the concerns for Southampton this season has been their home form, with just two wins at St Mary's in their last ten Premier League home games, and they haven't won any of their last four on home soil.
Shane Long is set to miss out once again with a broken metatarsal, picked up in the win at Middlesbrough, while Jeremy Pied could be in contention for a start with Cedric Soares and Ryan Bertrand both doubtful.
Meanwhile, Stoke could finish anywhere from 11th to 17th on the final day, with the Potters not finishing below 14th since their promotion to the Premier League in 2008.
Mark Hughes' men, who took three points away from St Mary's last season, are looking to arrest a dismal run of form with just one win in 10.
Austrian international Marko Arnautovic is set to face a late fitness test on an elbow injury, suffered in Stoke's 4-1 defeat to Arsenal last week. Ibrahim Afellay and Stephen Ireland remain long-term absentees.
These two teams also met here on the last day of the 2012-13 season, with Ricky Lambert cancelling out Peter Crouch's header in a 1-1 draw.