Manchester United have £89m signing Paul Pogba available after he served a suspension carried over from his time at previous club Juventus.
Defender Chris Smalling is also back following a ban and could return in place of Daley Blind.
Southampton captain Jose Fonte, who has been linked with United, could feature despite missing their opener because of a late start to pre-season.
Ryan Bertrand remains injured so Matt Targett will continue at left-back.
MOTD COMMENTATOR’S NOTES
Steve Wilson: “It has been 20 years since anyone with the tag of ‘the world’s most expensive player’ was at an English club – back then Newcastle had beaten Manchester United to the signature of Alan Shearer.
“Whether Jose Mourinho will unleash Paul Pogba from the start remains to be seen. Pogba has had only the briefest of pre-seasons after France’s Euro 2016 campaign, but his mere presence is a signal of United’s intent.
“Yet again the Saints’ powers of recovery will be tested by the loss of good players and a good manager. In Claude Puel, has the club continued its knack of making inspired managerial appointments, in the same way as their academy continues to produce outstanding young talent?
“We shall see – but Old Trafford is probably not the place to judge.”
Southampton manager Claude Puel on speculation linking Jose Fonte with United: “There is no problem with Jose, it is just strange that this rumour comes just before the game at United.
“But he is a very good professional and he has played well in training… Jose has good experience, so he cannot be disturbed by this rumour but I am just surprised to hear this before the game, two days before the match.”
Southampton have recorded 1-0 wins on each of their last two visits to Old Trafford.
Prior to that, Saints had gone 27 years – spanning 19 league games – since their last league win away to United.
The Red Devils are unbeaten at home since losing to Southampton in January, a run of 11 matches in league and cup (W8, D3).
United conceded just nine home league goals last season – the best record in the top flight.
Zlatan Ibrahimovic has scored on his league debut in four different countries.
Saints conceded 19 league goals away from home last term – the second best record in the top flight behind Leicester, who let in 18.
However, Southampton have conceded in 13 consecutive Premier League games, their longest run without a clean sheet since November 2012 (a run of 21).
They scored a joint league-high 15 headed goals in the 2015-16 season (level with West Ham).
Their two top scorers last season – Graziano Pelle and Sadio Mane – both left this summer.
SAM (Sports Analytics Machine) is a super-computer created by @ProfIanMcHale at the University of Salford that is used to predict the outcome of football matches.