Claudio Ranieri’s side is now eight points adrift of safety having picked up just one win in 2019.
Victory for Saints will leave them further adrift with their goal difference comfortably the worst in the top flight.
Claudio Ranieri acknowledged Fulham’s trip to Southampton on Wednesday is “crucial” in their bid to avoid relegation from the Premier League.
Fulham is eight points from safety with 11 games to play and have the second-worst goal difference in the league.
With Chelsea, Leicester, Liverpool and Manchester City to play after this match.
Fulham desperately needs a win to potentially breathe new life into their survival bid.
Saints are one place and seven points above Fulham, having lost their previous two matches to Cardiff and Arsenal.
Manager Ralph Hasenhuttl says his side will be hoping to “surprise” Fulham.
Team News of Southampton vs Fulham
Saints are without striker Michael Obafemi, who is set to miss the rest of the season after a recurrence of a hamstring injury.
The 18-year-old Republic of Ireland international had just returned to action as a substitute against Arsenal on Sunday but is now facing a lengthy spell of rehabilitation.
Saints boss Ralph Hasenhuttl confirmed striker Danny Ings (hamstring) was not yet ready to come into contention, while midfielder Mario Lemina (abdominal) also continues his recovery.
Claudio Ranieri reported no fresh injury problems ahead of the Premier League trip to the south coast.
Andre-Frank Zambo Anguissa and Lazar Markovic both came on for the second half of the 3-1 defeat at West Ham, so could be in contention to start.
Defender Alfie Mawson continues his recovery from a long-term knee injury.
Provisional squad: Gunn, Vestergaard, Stephens, Targett, Bednarek, Valery, Romeu, Ward-Prowse, Armstrong, Redmond, Hojbjerg, McCarthy, Yoshida, Bertrand, Elyounoussi, Slattery, Austin, Gallagher
Provisional squad: Rico, Odoi, Chambers, Ream, Bryan, Sessegnon, Cairney, Nordtveit, Seri, Mitrovic, Babel, Fabri, Le Marchand, Christie, Zambo, Markovic, Ayite, Vietto.
Score prediction: Southampton 1-0 Fulham
TV channel and live stream, and online coverage
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But you can follow all the action with Standard Sport’s LIVE blog.
There have been 73 meetings between these two over the years with Southampton picking up 27 wins to Fulham’s 22.
Southampton are unbeaten in their last 19 home league games against Fulham (W13 D6) since a 1-2 loss in October 1935 (second tier).
Only against Coventry (22 games) have they ever had a longer unbeaten home run in their league history.