Injured Southampton captain Jose Fonte has not travelled with Claude Puel's 21-man squad for the Europa League match against Sparta Prague.
Midfielders Dusan Tadic and Harrison Reed plus winger Matt Targett have also remained in England.
Tadic, who broke his nose while on international duty, is also unlikely to play against Everton on Saturday.
But midfielder James Ward-Prowse, who missed the weekend's draw against Liverpool, has recovered from injury.
Striker Charlie Austin, defender Ryan Bertrand and midfielder Steven Davis have also been included in the squad.
Southampton are second in Group K and victory in Prague - combined with Hapoel Be'er Sheva failing to beat Inter Milan in the other tie of the group - will guarantee the Saints progress to the knockout stages with a game to play.