While sixth-placed Tottenham Hotspur are six spots above Southampton, the sides are only one point apart in a congested mid-table.
Both teams are seeking to bounce back from a defeat last weekend, against Leicester City and AFC Bournemouth respectively, and secure a third victory of the season.
Team news
Mauricio Pochettino has no fresh injury concerns ahead of the visit of his former club.
Only Giovani Lo Celso and Ryan Sessegnon remain sidelined for Spurs with a hip and hamstring problem respectively.
Southampton will assess the fitness of goalkeeper Alex McCarthy, who is doubtful with a muscle injury.
Moussa Djenepo (thigh) has been ruled out and manager Ralph Hasenhuttl says he does not know when the winger might return.
Did you know?
This will become only the second Premier League fixture to be played in five different stadiums: Wembley, White Hart Lane, the Tottenham Hotspur Stadium, St Mary's and The Dell. The other match is Spurs versus West Ham, which the Hammers have hosted at the Boleyn Ground and London Stadium.
Spurs' last eight Premier League victories have come at home. They last had a longer run of wins exclusively at home between April 2000 and January 2001, with 10.
Southampton are looking to win three consecutive top-flight away matches for the first time since February 2015, when they had a run of four, while they last did so without conceding in April 1992.
Spurs have won seven of their last eight PL home matches against Southampton, losing the other 2-1 in May 2016.
Match officials
Referee: Graham Scott. Assistants: Neil Davies, Derek Eaton. Fourth official: Darren Bond. VAR: Darren England. Assistant VAR: Ian Hussin.
