New Baggies boss Pepe Mel will watch from the stands following his appointment Thursday as Keith Downing takes charge of the team for the last time at St. Mary's Stadium.
Mauricio Pochettino's side has only won once in the Premier League since Nov. 9, a run that has seen the club fall from third to ninth in the table.
West Brom, meanwhile, has enjoyed an upturn in fortunes after four consecutive league defeats saw coach Steve Clarke relieved of his duties in December. Under the caretaker stewardship of Keith Downing, the Midlands club has picked up six points from four league games to climb up to 14th.
Saturday's match will represent Downing's last in charge, however, following the appointment of Mel as Clarke's permanent successor on Thursday.
The 61 previous league meetings between West Brom and Southampton have seen both sides claim 21 victories apiece. Southampton ran out 1-0 winners at the Hawthorns on the opening day of the season, courtesy of a last-minute penalty from Rickie Lambert.
The striker is one of several Saints players to have been troubled by injury recently, but the south coast club is starting to get players back and Pochettino hopes to have goalkeeper Artur Boruc (hand) available Saturday.
"He may play or he may not play," the 41-year-old told reporters, before offering updates on other members of his squad.
"Victor [Wanyama] is still far off; he is still not fit," Pochettino continued. "Guly [Do Prado] has been training very well and is coming to the end of his recovery process. Gaston [Ramirez] and Lambert had knocks against Burnley and they are recovering well as well. It is very important we are slowly but surely getting back the players that have been missing over the last month."
The hosts will be without Dani Osvaldo through suspension, while West Brom has no new injury worries. Victor Anichebe (groin), Billy Jones (head) and Youssuf Mulumbu (eye) are all back in contention, while Shane Long is expected to feature despite reports linking him with a move away.