The strikers are absent from Boro's matchday squad after picking up knocks in training last week, meaning that Christian Stuani and Jordan Rhodes come into the side to join Viktor Fischer in the front line.
For the hosts, Claude Puel makes five changes from the side that suffered a 3-0 defeat at relegation-threatened Crystal Palace a week ago, with Charlie Austin ruled out of the clash after picking up a shoulder injury in the side's midweek Europa League game with Hapoel Be'er Sheva.
Southampton: Forster; Martina, Fonte, Van Dijk, McQueen; Ward-Prowse, Romeu, Clasie; Rodriguez, Tadic, Boufal
Subs: Taylor, Yoshida, Long, Davis, Reed, Bertrand, Redmond
Middlesbrough: Valdes; Barragan, Chambers, Gibson, Fabio; Clayton, De Roon, Forshaw; Stuani, Fischer, Rhodes
Subs: Guzan, Bernardo, Nsue, Leadbitter, Traore, Downing, Nugent