Marco Silva has made a staggering nine changes to his team following a disappointing 1-0 defeat against West Ham United in the Premier League earlier this week.
It is a massive shake-up, with the Hatters bidding to reach consecutive FA Cup quarter-finals this afternoon.
Captain Tom Cairney and winger Samuel Chukwueze are the only players to keep their spots in the starting line-up.
Harry Wilson does not feature in the squad after picking up a knock against Tottenham.
Fulham XI: Lecomte, Castagne, Andersen, Cuenca, Sessegnon, Reed, Cairney, Smith Rowe, Bobb, Muniz, Chukwueze
Subs: Leno, Tete, Bassey, Robinson, Berge, Lukic, King, Iwobi, Raul
Southampton boss Tonda Eckert chooses to make four changes to his side, who are currently nine games unbeaten in all competitions.
The Saints’ strong run of form has seen them make a late push for the Championship play-off spots – and they will be hoping to continue that run at Craven Cottage.
Jack Stephens and Shea Charles miss out on the matchday squad altogether, while Cam Bragg and Kuryu Matsuki drop to the bench.
Southampton XI: Peretz, Bree, Wood, Harwood-Bellis, Manning, Downes, Jander, Fellows, Azaz, Scienza, Larin
Subs: Long, Quarshie, Jelert, Romeu, Bragg, Matsuki, Edozie, Archer, Stewart
