The Saints club-record signing Gaston Ramirez could feature on the bench but could make a late appearance as manager Nigel Adkins is likely to start with last season's Championship's top-scorer Ricky Lambert. Jay Rodriguez and Tadanari Lee are probables to start on the flanks in a 4-3-3 system.
Southampton are likely to retain the same back-four while Steven Davis seems to have cemented his place in the starting XI.
The Red Devils boss Sir Alex Ferguson may not take the risk of brining in Jonny Evans, who returned to training after playing with the reserve squad, as Michael Carrick is set to continue to partner Nemanja Vidic in central defence.
Right-back Rafael is set for a comeback meaning Anotnio Valencia could replace Nani at right wing while Ashley Young and Shinji Kagawa will play behind lone striker Robin van Persie.
United have an excellent record at St Mary's winning all matches in their last four visits. However, Southampton have 38 percent of matches at home against the Red Devils.
*Manchester United have lost three out of last four matches away from home.
*Southampton have won 27 out of their last 36 home games.
*The Saints beat Manchester United 6-3 during the Premier League season in 1996-97.
Southampton (4-3-3): Davis-Clyne, Hooiveld, Fonte, Fox-Davis, Schneiderlin, Lallana-Rodriguez, Lambert, Lee.
Manchester United (4-2-3-1): De Gea-Rafael, Carrick, Vidic, Evra-Cleverley, Anderson-Valencia, Kagawa, Young-Van Persie