Enzo Maresca's side continued their excellent run of form with another eye-catching win at the weekend, while the hosts remain cut adrift at the bottom following some controversy on Friday.
Match preview
Following a 3-0 win over Aston Villa on Sunday, whispers of Chelsea being in the title race have gotten slightly louder.
Maresca's men have arguably been the most impressive team in the Premier League behind runaway leaders Liverpool, with Sunday's success keeping them in tied-second with Arsenal, with alphabetical order the only thing that has the Gunners above them in the table.
With their attacking players all firing and a first league clean sheet since mid-September, it was a perfect afternoon for the Blues, who continue to make a mockery of their pre-season doubters.
Both Maresca and talisman Cole Palmer rubbished any talk of being in the title race post-match on Sunday though, with the midfielder admitting it will be tough given that this is the first year of their project, given that players are still bedding in.
This midweek fixture will give them an excellent opportunity to potentially move into second outright though, with Arsenal facing a tricky test against Manchester United.
Chelsea have won all four away games against sides in the bottom half so far this season, and with 10 defeats in 13 so far, Southampton appear favourable opponents on paper.
However, the hosts have a good recent record against Chelsea, losing just twice in the last seven meetings, and completing a league double over them when they were relegated in 2022-23.
Russell Martin's men can also take plenty of positives from a spirited display at Brighton & Hove Albion on Friday that ended in a 1-1 draw.
Frustration was high in the aftermath though, with Martin absolutely furious that Cameron Archer's potential winner was controversially disallowed by VAR.
It was a second impressive performance in the space of a week for the Saints, who came so close to taking points off Liverpool five days earlier, but fell to a 3-2 defeat.
Results just have not been coming their way, with the 1-0 home win over Everton still their only success of the season so far.
Fixtures continue to get tricky for Martin's side too, with Chelsea and Tottenham Hotspur to come at St Mary's, and trips to European-chasing Aston Villa and Fulham before Christmas.
Opta seem to suggest that it will be too much of an uphill struggle for the side four points adrift at the bottom, with their predictions giving Southampton a 94% chance of being relegated.
Underlying stats prove the reasons why, because not only have they scored the fewest goals in the Premier League, Southampton have also made the most errors leading to shots and goals, and lost possession in the defensive third more often than any other side, something which Martin himself has come under scrutiny for.
Southampton Premier League form:
L
L
W
L
L
D
Southampton form (all competitions):
L
W
W
L
L
D
Chelsea Premier League form:
L
W
D
D
W
W
Chelsea form (all competitions):
D
W
D
W
W
W
Team News
Southampton could have as many as 11 players missing due to injury, suspension and ineligibility here, with bookings for Taylor Harwood-Bellis, Tyler Dibling and Flynn Downes on Friday triggering bans.
Lesley Ugochukwu also cannot play against his parent club, while thigh injuries for Will Smallbone and Adam Lallana are set to rule the midfield pair out.
Goalkeeper Aaron Ramsdale remains out, so Joe Lumley should keep his place after making his Premier League debut at the age of 29 on Friday, replacing Alex McCarthy, who looked uncomfortable and made a huge error in the defeat to Liverpool.
Chelsea will be without defender Wesley Fofana for around four-to-five weeks after he sustained a hamstring injury in the win over Villa on Sunday.
Fofana joins Reece James on the sidelines, with a hamstring problem also keeping the right-back out, but apart from that, Maresca has the rest of his squad available to him here, following the returns of Malo Gusto and Pedro Neto at the weekend.
Being able to rotate in cup competitions means Chelsea's league XI should still be feeling fresh, so there may be few personnel changes at St Mary's, but Noni Madueke could be one, after he was surprisingly left out of the side at the weekend.
Southampton possible starting lineup:
Lumley; Sugawara, Walker-Peters, Wood, Stephens, Manning; Fraser, Aribo, Mateus Fernandes, Armstrong; Archer
Chelsea possible starting lineup:
Sanchez; Gusto, Badiashile, Colwill, Cucurella; Caicedo, Enzo; Madueke, Palmer, Neto; Jackson
We say: Southampton 1-4 Chelsea
Southampton have certainly improved in recent weeks, but their style of play means they will give up chances, and Chelsea have proven they are a clinical force in attack so far this season.