While the Blues have won only one of their nine fixtures in all competitions since the turn of the year, the Saints have lost nine of their last 10 top-flight games.
Match preview
Although head coach Graham Potter seemingly has the support of Chelsea's hierarchy, a torrid run of just three victories in their last 16 matches across all competitions is a major cause for concern.
After drawing three successive Premier League games against Liverpool, Fulham and West Ham United, the Blues suffered a slender 1-0 defeat away against Borussia Dortmund in the first leg of their Champions League last-16 tie on Wednesday, with Karim Adeyemi scoring a stunning solo goal in the 63rd minute.
Once again, Chelsea lacked a cutting edge in the final third and despite spending over £600m on new recruits in the last two transfer windows, the failure to bring in a natural number nine has come back to haunt them. Indeed, the West Londoners have scored in only five of their last 14 matches across all tournaments, while they have found the net just 23 times in 22 Premier League games so far this term.
Momentarily putting Champions League exploits to one side, Potter and co head into Saturday's Premier League fixture sitting 10th in the table - their lowest position at this stage of a top-flight season for seven years - and 10 points behind Newcastle United in fourth.
Chelsea can ill-afford to drop any more points if they wish to keep their slim hopes of securing a top-four spot alive, although claiming maximum points against Southampton could prove challenging as they have failed to win three of their last four league meetings with the Saints at Stamford Bridge.
After just three months in charge - one of which was during the World Cup break - Nathan Jones was relieved of his duties as Southampton boss last Sunday, less than 24 hours after the Saints lost 2-1 at home to 10-man Wolverhampton Wanderers.
Southampton appeared to be on course to claim three valuable points heading into the final 20 minutes, leading 1-0 courtesy of a first-half strike from Carlos Alcaraz, but an own goal from Jan Bednarek and an 87th-minute winner from Wolves' Joao Gomes turned the game on its head to condemn the Saints to their 15th league defeat of the season.
Jones departs Southampton after losing nine of his 14 games in charge, leaving them at the foot of the table and four points adrift of safety, and the search for his successor continues after talks with former Leeds United head coach Jesse Marsch broke down earlier this week.
In the meantime, Ruben Selles has been placed in temporary charge of the first team for this weekend's trip to Stamford Bridge and the 39-year-old will be hoping his side can replicate the performance in their last meeting with Chelsea earlier this season.
Indeed, the second of four Southampton victories in the Premier League this season came against Chelsea back in August when goals from Romeo Lavia and Adam Armstrong secured a 2-1 victory at St Mary's, and the Saints will complete their first league double over the Blues since the 1987-88 campaign if they come out on top again on Saturday.
Chelsea Premier League form:
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L
W
D
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D
Chelsea form (all competitions):
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W
D
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L
Southampton Premier League form:
L
L
W
L
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Southampton form (all competitions):
L
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W
L
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L
Team News
Chelsea are still having to cope without injured quartet N'Golo Kante (thigh), Christian Pulisic (knee), Armando Broja (knee) and Edouard Mendy (finger), while Raheem Sterling (knee) and Ben Chilwell (knock) are both doubtful.
Mateo Kovacic, Wesley Fofana and Denis Zakaria all recovered from injury to feature in the matchday squad against Dortmund and the trio will be in contention to start against Southampton.
Benoit Badiashile, Noni Madueke, Pierre-Emerick Aubameyang and David Datro Fofana, who were all ineligible in midweek after being left out of the Champions League squad, are all available for selection on Saturday, with the former expected to replace Kalidou Koulibaly at centre-back.
Madueke, meanwhile, could start on the right-flank at the expense of Hakim Ziyech, joining Joao Felix, Mykhaylo Mudryk and Kai Havertz in attack.
As for Southampton, Valentino Livramento (knee), Alex McCarthy (ankle) and Juan Larios (hamstring) all remain sidelined, but Kyle Walker-Peters could return to the first-team fold after missing the last two matches with a hamstring injury.
Mislav Orsic, Duje Caleta-Car, Mohamed Elyounoussi, Ibrahima Diallo and Armel Bella-Kotchap will all be hoping to return this weekend after being left out of the matchday squad against Wolves for tactical reasons.
Ainsley Maitland-Niles was surprising used in the back three last weekend, but either Caleta-Car, Bella-Kotchap or Lyanco will likely replace the Arsenal loanee, while Bednarek and Mohammed Salisu are set to retain their places in the first XI.
Club-record signing Kamaldeen Sulemana showed glimpses of his quality against Wolves and he is expected to continue in attack, while Che Adams will be pushing to start ahead of Paul Onuachu.
Chelsea possible starting lineup:
Arrizabalaga; James, Thiago Silva, Badiashile, Cucurella; Loftus-Cheek, Fernandez; Madueke, Felix, Mudryk; Havertz
Southampton possible starting lineup:
Bazunu; Caleta-Car, Bednarek, Salisu; Walker-Peters, Lavia, Ward-Prowse, Alcaraz, Perraud; Sulemana, Adams
We say: Chelsea 2-1 Southampton
Three valuable points are up for grabs at Stamford Bridge on Saturday and both teams are in desperate need of a victory in their quest to turn their fortunes around.