Both sides sit in the bottom four of the table after 11 games, with the Saints in the relegation zone and Everton three points but only one place better off than their weekend hosts.
It promises to be a significant weekend at the wrong end of the table as the bottom four all face each other, with this match being preceded by a battle of the basement two when Norwich City host winless Watford on Friday night.
The Canaries are perhaps the only one of the quartet that most fans would have expected to see in and around the danger zone at this stage of the campaign, although consecutive finishes of 17th and 16th for Southampton in the last two seasons suggested that they might be up against themselves too.
Certainly, Ralph Hasenhuttl's side can have no complaints at sitting in the bottom three at the moment, having picked up only one point from their last six league outings - including the already-infamous 9-0 humiliation at home to Leicester City.
There was a marked improvement last weekend as Southampton came within four minutes of taking points off champions Manchester City at the Etihad, but Saturday's game is their first at home since the Leicester debacle and the St Mary's crowd will be demanding another response.
Southampton's home stats do not exactly inspire confidence, though; they have picked up only one point in front of their own fans this season and could become only the second team in Premier League history to amass one point or fewer from their first six home games of a campaign, while they have already conceded 19 goals on home turf - the most by a top-flight team after five games since 1930-31.
It is unsurprising that Hasenhuttl's future has come under scrutiny, then, and should they fall to a fourth successive home league defeat - a fate which has never befallen them at St Mary's and last did so more than 21 years ago at The Dell - then the Austrian could find himself living on borrowed time.
Marco Silva will sympathise with his opposite number having seen his own future called into question on numerous occasions already this season, although there is no doubt that the Toffees have underperformed so far following a significant summer outlay on transfers.
Everton begin the weekend 17th in the standings having been tipped to push for the top six back in August, largely due to a run of five defeats and just one win from their last seven Premier League games.
Last weekend's stoppage-time equaliser against Tottenham Hotspur was overshadowed by the sickening injury suffered by Andre Gomes earlier in the match, but it could prove to be a valuable point and at least keeps them safe from dropping into the relegation zone this weekend - barring a six-goal Southampton win.
Silva will also no doubt be stressing that a couple of positive results could completely change the outlook of their season - the Toffees may only be one place above the bottom three, but in terms of points they are actually closer to the top half than they are to Saturday's opponents.
Back-to-back wins could make a huge difference to the table, then, and Everton must be viewing this game and their first match after the international break - against 19th-placed Norwich - as a golden chance to get those, particularly with Leicester City, Liverpool, Chelsea, Manchester United and Arsenal to come in succession after that - a devilishly difficult run-up to Christmas.
The main issue for Silva to solve is Everton's away form; they have lost their last four top-flight games on the road and have picked up just one point on their travels this term - that coming on the opening day of the season.
Indeed, this contest pits the worst home record in the league against the joint-worst away record, so it could be that the head-to-head record between the two sides offers most clues about which way this one will go.
In that respect, Southampton will feel confident. The Saints have won five of their last six Premier League home games against Everton, while 11 of their 12 victories over the Toffees in this competition have come in front of their own fans.
Either way, one poor record is likely to end this weekend, with victory providing a potentially priceless lifeline for one manager and a potentially fatal nail in the coffin for the other.
Southampton Premier League form: LLLDLL
Southampton form (all competitions): LLDLLL
Everton Premier League form: LLLWLD
Everton form (all competitions): LLWLWD
Gomes will be sidelined for a lengthy period after breaking and dislocating his ankle against Tottenham last weekend - an injury which left both sets of players visibly distressed at Goodison Park.
Silva suggested that the Portuguese midfielder might still play again this season, but for now his absence could provide Gylfi Sigurdsson with a route back into the starting lineup on a regular basis.
Gomes joins Jean-Philippe Gbamin on the list of long-term absentees for Everton, while Fabian Delph could also miss Saturday's match due to a tight hamstring and Bernard will not return until after the international break.
Theo Walcott will be hopeful of another start against his former club, having scored five goals and assisted another in his last four appearances against the Saints.
Southampton are still without the suspended Ryan Bertrand following his red card against Leicester, but they may be able to welcome Cedric Soares back into the fold for the first time since September.
The defender announced his intention to leave the club at the end of the season earlier this week but could be called upon as an emergency left-back after Pierre-Emile Hojbjerg was forced into the unfamiliar role at Man City.
Alex McCarthy was recalled in goal for that match and will hope to have done enough to keep his place behind what is likely to be a largely unchanged team from the narrow defeat.
Southampton possible starting lineup:
McCarthy; Bednarek, Stephens, Vestergaard; Valery, Ward-Prowse, Romeu, Hojbjerg, Cedric; Ings, Redmond
Everton possible starting lineup:
Pickford; Sidibe, Mina, Holgate, Digne; Schneiderlin, Davies; Walcott, Sigurdsson, Iwobi; Richarlison
We say: Southampton 1-2 Everton
This match pits the worst home record against the joint-worst away record in the league, and something surely has to give. Both sides have been poor this season, but Everton have been marginally better and certainly have enough quality in their ranks to beat a Southampton side devoid of confidence. The visitors will also be eager to get a result for Andre Gomes, which might be enough to spur them on to a rare away win at the Saints.