Ronald Koeman has named 19-year-old midfielder Harrison Reed a first Premier League start as he looks to end a run of six matches without a win.
With Victor Wanyama and Morgan Schneiderlin both suspended, and Jack Cork injured, the Dutch coach has had to look to his youngsters to fill in.
England Under-21 international James Ward-Prowse, 20, also starts while Toby Alderweireld could complete a midfield that is also without Dusan Tadic.
Shane Long starts up front alongside Graziano Pelle but there are five academy players on the bench.
Roberto Martinez has made two changes to the team that beat Queens Park Rangers on Monday, with Gareth Barry and Samuel Eto'o coming in for Aiden McGeady, who drops to the bench, and the injured Kevin Mirallas.
Southampton: Forster, Clyne, Yoshida, Fonte, Bertrand, Alderweireld, Davis, Ward-Prowse, Reed, Long, Pelle.
Subs: Davis, Mane, McCarthy, Targett, McQueen, Seager, Gape
Everton: Howard, Coleman, Distin, Jagielka, Baines, Besic, Barry, Barkley, Naismith, Eto'o, Lukaku.
Subs: Robles, McGeady, Kone, Pienaar, Stones, Garbutt, Alcaraz.Reuse content