The Cottagers have managed one win in 30 league visits to Southampton - a 2-1 victory in the second tier back in October 1935 - and are winless in nine such meetings.
Ahead of this latest encounter on the South Coast, Sports Mole rounds up all of the latest team news for the two clubs.
Sports Mole's predicted XI: McCarthy; Walker-Peters, Salisu, Vestergaard, Stephens; Walcott, Armstrong, Ward-Prowse, Djenepo; Redmond, Adams
Sports Mole's predicted XI: Areola; Aina, Andersen, Adarabioyo, Robinson; Loftus-Cheek, Anguissa; Cavaleiro, Onomah, Lookman; Maja
Watch the Sports Mole Football Shorts prediction for this game below: