Exeter are boosted by the return of centre-half Troy Archibald-Henville after signing on a permanent deal from Tottenham Hotspur.Defender Rob Edwards and strikers Joe Burnell and Barry Corr will all be vying for a place in the Exeter team.
Southampton will again be without midfielder Dean Hammond (Achilles) but midfield pair Adam Lallana and Lloyd James are both fit.
New signing Jason Puncheon is set for his debut after signing from Plymouth.