The Blues have picked up maximum points from their last four league matches to move into fourth position in the table, while Southampton have dropped to 13th following six straight losses in England's top flight.
Southampton's Premier League form is concerning, with the Saints now losing each of their last six since recording a 1-0 win over Liverpool at the start of January.
Ralph Hasenhuttl's side managed to progress to the quarter-finals of the FA Cup on February 11 with a 2-0 win at Wolverhampton Wanderers but then lost 2-1 to the same opposition in the league last weekend.
Southampton looked like they would challenge for a Europa League spot in the latter stages of 2020, but a poor run of form has seen them drop into 13th position in the table, now 11 points behind sixth-placed Liverpool.
The Saints are only actually four points clear of 17th-placed Newcastle United, meanwhile, and they now face three tough fixtures against Chelsea, Leeds United and Everton.
Hasenhuttl's side have taken four points from their last two league matches with Chelsea, though, and held the Blues to a 3-3 draw when the two teams locked horns at Stamford Bridge back in October.
Southampton might be struggling to halt a losing run, but the same cannot be said for Chelsea, who have been in impressive form since Thomas Tuchel replaced Frank Lampard as head coach at the end of January.
The Blues have won five of their six matches under their new manager, including four straight victories in the Premier League against Burnley, Tottenham Hotspur, Sheffield United and Newcastle United to rise into fourth.
Chelsea are level on points with fifth-placed West Ham United and just two points clear of sixth-placed Liverpool, but they are also only four points off second-placed Manchester United on the same number of matches, which is an indication of how much of a turnaround has occurred.
The capital giants will face Atletico Madrid in the first leg of their last-16 Champions League clash on February 23 before the small matter of a home league match against Man United at the end of the month.
The Blues only have the seventh-best away record in the Premier League this term, dropping points in six of their 12 matches, but they have won at Tottenham and Sheffield United since Tuchel's arrival.
Southampton Premier League form: LLLLLL
Southampton form (all competitions): LLLLWL
Chelsea Premier League form: LDWWWW
Chelsea form (all competitions): DWWWWW
Southampton boss Hasenhuttl confirmed during Thursday's press conference that Kyle Walker-Peters is out for "a few weeks" through injury, while Ibrahima Diallo and Theo Walcott remain sidelined for the clash.
As for Chelsea, Tammy Abraham is a slight doubt with the ankle problem that he picked up against Newcastle on Monday evening, and the striker could be protected ahead of some important fixtures, meaning that Olivier Giroud might get the nod through the middle.
Thiago Silva and Kai Havertz were both back in training on Thursday, but the former will not be involved at St Mary's as Tuchel looks ahead; Andreas Christensen should therefore continue at the heart of the defence, with Marcos Alonso again potentially getting the nod over Ben Chilwell as the left-sided wing-back.
Southampton possible starting lineup:
McCarthy; Stephens, Bednarek, Vestergaard, Bertrand; Armstrong, Romeu, Ward-Prowse, Minamino; Adams, Ings
Chelsea possible starting lineup:
Mendy; Azpilicueta, Christensen, Rudiger; Hudson-Odoi, Jorginho, Kovacic, Alonso; Mount, Giroud, Werner
We say: Southampton 0-1 Chelsea
Southampton are certainly capable of making it a difficult afternoon for Chelsea despite the fact that they are currently struggling for form. The Blues are on a bit of a roll at the moment, though, and we expect them to pick up another three points to hand their top-four hopes a huge boost.
Watch the Sports Mole Football Shorts prediction for this game below: