Southampton full-back Ryan Bertrand will miss the season opener against Watford because of a knee injury.
New Southampton manager Claude Puel has favoured a midfield diamond during pre-season, with Shane Long and Nathan Redmond set to start in attack.
Watford head coach Walter Mazzarri will be without new signings Brice Dja Djedje and Isaac Success because of respective foot and leg injuries.
Craig Cathcart is nursing a back problem but is expected to play.
MOTD COMMENTATOR'S NOTES
Tony Husband: "New managers, new formations and some new players will be on show at St Mary's for a clash of two clubs accustomed to change.