Southampton make the trip to Stamford Bridge having suffered back-to-back defeats, but the Saints remain out of the relegation zone on goal difference.
The manner of Chelsea's victory against Crystal Palace epitomised what Maurizio Sarri has brought to the club since his arrival in July, but the Blues still remain levels below the Italian's expectations.
A total of 15 points from a possible 21 during December - a month which has also included Europa League and EFL Cup matches - is an excellent return for a group of players who have not necessarily been excessively rotated by Sarri, but Chelsea are still looking for that killer touch in front of goal.
A second-half effort from N'Golo Kante proved to be the difference at Selhurst Park and although another win was all that mattered, Chelsea failed to make the most of their domination, with Palace not registering a shot on goal until the closing stages.
That said, a number of injuries may result in Sarri finally having to tinker with his tried-and-trusted starting lineup given that Chelsea have four games to play in the space of 11 days up until January 12.
Five of Sarri's squad have started in each of the club's 20 Premier League fixtures this season with David Luiz and Jorginho missing just one apiece, and Sarri must begin to weigh up resting those players with the possibility of more than a dozen cup ties still to come during this campaign.
A balance will have to be found with Champions League qualification remaining the priority, but Sarri will also be desperate to end his wait for silverware as a manager.
Arsenal's recent demise has given Chelsea a five-point cushion in the race for a top-four spot, and that may just lead to the former Napoli man taking a chance on some of his squad members during this upcoming period.
Recent form: LWWLWW
Recent form (all competitions): DWWLWW
Home matches in quick succession against an in-form West Ham United and Pep Guardiola's Manchester City were never going to be an easy task, but Ralph Hasenhuttl will be disappointed that no points were recorded from the St Mary's double-header.
The games came after hugely impressive wins against Arsenal and Huddersfield Town - results which lifted the club out of the relegation zone - but Hasenhuttl must now regroup and reassess ahead of January.
There is an inevitability of new players coming through the door and squad members being allowed to leave, but the Austrian will have to find a balance between reacting to successive setbacks and identifying which positions require a fresh face.
Southampton fans remain optimistic about the future under Hasenhuttl, although it is important that more points are acquired from games against Chelsea, Leicester City and Everton given the fixtures which follow.
The south-coast outfit take on Crystal Palace, Burnley and Cardiff City all in the space of 10 days, and there will be an acknowledgement that those games could make or break the club's future.
A priority for Hasenhuttl will be to improve his team's defensive record in the top flight with no clean sheet being recorded since October 27 and nine goals being conceded in his opening five matches in the dugout.
The former RB Leipzig boss has brought back excitement at a club which had been struggling in the final third for some time, but Southampton are unlikely to avoid relegation to the Championship if they ship goals at a rate of two per game.
Hasenhuttl will tell his players that they have the freedom to express themselves on Wednesday night with all of the pressure on Chelsea's shoulders, but the foundations must be put in place at the back and Southampton already know that they were fortunate to only concede three times when the teams met in October.
Recent form: LLWWLL
Pedro will remain on the sidelines with a hamstring injury, while Callum Hudson-Odoi is a huge doubt due to carrying a similar problem and the youngster may be rested until Saturday's FA Cup tie with Nottingham Forest to give Eden Hazard or Willian a weekend off.
Chelsea possible starting lineup:
Arrizabalaga; Azpilicueta, Rudiger, Luiz, Alonso; Kante, Jorginho, Kovacic, Willian, Morata, Hazard
Southampton possible starting lineup:
McCarthy; Yoshida, Stephens, Bednarek; Valery, Lemina, Romeu; Targett; Armstrong, Redmond, Ings
Head To Head
Wednesday's meeting will represent the 104th competitive encounter between the two clubs, with Chelsea winning 45 times in comparison to 30 victories for Southampton.
The Saints went through a period between 2013 and 2015 where they only suffered three defeats in eight outings against the West Londoners, but that has changed in recent years.
Chelsea have prevailed in each of the last seven matches in all competitions with 17 goals being scored during those fixtures.
We say: Chelsea 2-1 Southampton
Chelsea have failed to score more than two goals in a Premier League match for two months, and that may continue on Wednesday evening due to their mounting injury list. However, the Blues have also won a number of tight contests and we are backing Sarri's men to do the same in this game.