Saints manager Ronald Koeman revealed the midfielder sustained ankle ligament damage in Wednesday’s defeat at Arsenal, when Toby Alderweireld was forced off with a hamstring complaint which makes him a doubt.
Morgan Schneiderlin is unavailable, as are long-term absentees Jay Rodriguez (knee), James Ward-Prowse (foot) and Sam Gallagher (knee), but Dusan Tadic has overcome a knock.
Wayne Rooney will be fit to face Southampton on Monday, Manchester United manager Louis van Gaal has confirmed.
Captain Rooney had a scan on Thursday to examine a possible knee problem but has been given the all-clear. However record signing Angel di Maria will not be ready to return from his hamstring injury in time for the trip to the south coast.
Luke Shaw (ankle), Jonny Evans (ankle), Rafael (groin), Daley Blind (knee) and Phil Jones (calf) are all expected to miss out.