Just one point separates the two sides in the table after four games of the season, and both teams head into this contest off the back of victories before the two-week stoppage.
It has been a topsy-turvy start to the season for Chelsea, who go into this weekend sitting seventh in the table with seven points to their name - already five points adrift of early pace-setters Everton.
Frank Lampard will be feeling a lot better about his side's chances following their 4-0 victory over Crystal Palace before the international break as the unlikely trio of Ben Chilwell, Kurt Zouma and Jorginho (twice) got on the scoresheet.
Four goals in a game is always a welcome sight, but in what was their first league outing since the 3-3 draw with West Bromwich Albion it was arguably the clean sheet which would have pleased Lampard the most as new signing Edouard Mendy brought about an immediate improvement.
The summer arrival was admittedly rarely tested, though, and he will not feature in this match after picking up an injury on international duty with Senegal, which could mean a swift recall for the under-fire Kepa Arrizabalaga.
Surprisingly, though, no team involved in both of the last two Premier League campaigns has conceded fewer home goals than Chelsea since the start of last season, underpinning a good run of form at Stamford Bridge recently.
The Blues may have lost eight times at home across all competitions last season, and they have already been beaten there by Liverpool this term, but they go into Saturday's match having won seven of their last eight league games on their own patch by an aggregate scoreline of 18-4.
Indeed, Chelsea have kept clean sheets in five of their last six home outings across all competitions and have won their last two by a 10-0 aggregate score, although Southampton have every reason to be confident of blemishing that recent record.
The Saints won at Stamford Bridge last season - their only triumph in their last nine top-flight meetings with Chelsea - and could now win back-to-back league games away to Chelsea for the first time since March 1985.
Successive victories to nil before the international break suggest that they have the means to do exactly that, with triumphs over Burnley and West Brom getting Southampton off the mark after a false start.
Not since January 2016 have the Saints won three successive Premier League matches without conceding, and doing so would be the perfect reaction to their 5-2 home defeat at the hands of Tottenham Hotspur last month.
Ralph Hasenhuttl's side have now won six and lost only two of their last 11 top-flight outings, and last season in particular they carved out a reputation as away specialists.
Indeed, their opening-day loss at the hands of Crystal Palace is their only Premier League away defeat since February, so if Chelsea happen to have one eye on their Champions League opener against Sevilla on Wednesday then an upset could be in the offing.
Chelsea Premier League form: WLDW
Chelsea form (all competitions): WLWDLW
Southampton Premier League form: LLWW
Southampton form (all competitions): LLLWW
Chelsea will be without two of their summer signings for this match, with Lampard confirming that neither Mendy nor Thiago Silva will feature following their international exertions.
Mendy picked up a thigh injury during his time away with Senegal, while Silva has been ruled out due to the amount of travelling he did while away with Brazil over the last two weeks.
Ben Chilwell was forced to pull out of England's squad, but Lampard has said that he is "available" in an added boost to his squad with a number of other players also returning.
Tammy Abraham will hope to lead the line from the start again, but Olivier Giroud could be an option off the bench having netted seven times against Southampton before, the last four of which have all come as a sub.
There are also decisions to be made elsewhere with Mateo Kovacic pushing for a return but Jorginho having scored three times already this season - just one short of his final tally for the whole of 2019-20.
N'Golo Kante picked up an injury on international duty which saw him miss France's win over Kovacic's Croatia on Wednesday, though, and that could lend itself to a straight swap between the pair if Kante does not pass a late fitness test.
Silva's absence could lead to a first appearance of the season for Antonio Rudiger after he stayed at the club on deadline day, but Lampard may otherwise stick with the same defensive quartet that kept a clean sheet against Crystal Palace, meaning no start for England's newest debutant Reece James.
Southampton are not quite blessed with as many selection headaches, with Stuart Armstrong ruled out after testing positive for coronavirus.
New signing Mohammed Salisu is yet to feature as he recovers from injury, and this match will also come too soon for the centre-back.
There could be debuts for deadline day arrivals Theo Walcott and Ibrahima Diallo, with the prodigal son Walcott in line for his second debut for the club from the start due to the absence of Armstrong and the injured Moussa Djenepo.
Danny Ings will lead the line, having wasted no time in picking up where he left off last season with three goals in his four league games so far, while Nathan Redmond could make his first league start of the season.
Chelsea possible starting lineup:
Kepa; Azpilicueta, Christensen, Zouma, Chilwell; Jorginho, Kovacic; Mount, Havertz, Pulisic; Werner
Southampton possible starting lineup:
McCarthy; Walker-Peters, Bednarek, Vestergaard, Bertrand; Walcott, Ward-Prowse, Romeu, Redmond; Ings, Adams
We say: Chelsea 2-1 Southampton
Ings will fancy his chances of scoring against Kepa in this match and Southampton certainly have both the quality and momentum to cause Chelsea problems here.
However, with the Blues very nearly now up to full strength in terms of their attacking options, we expect the hosts to have enough firepower to pick up all three points.
Top betting tipOur expert tipster partners at Sporita.com are predicting over 2.5 goals in this match. Click here to find out what else they are predicting for this game and for more of their tried-and-tested football tips.Over 2.5:data
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