The Gunners have suffered back-to-back losses since returning to Premier League action, whereas Southampton picked up victory against Norwich City in their first game back.
The same old questions have been asked of Arsenal's mental strength after once again throwing away victory in Saturday's trip to Brighton & Hove Albion.
Mikel Arteta's side led 1-0 at the Amex Stadium through Nicolas Pepe's wonder strike, only for Lewis Dunk to equalise 15 minutes from time and Neal Maupay to snatch all three points for Brighton deep into added time.
The defeat to Brighton came three days on from a pretty routine 3-0 loss at Manchester City, with the reigning champions not really having to move out of second gear to pick up the win.
Having been on an 11-game unbeaten run on their travels in all competitions, then, it is now back-to-back away defeats for the Gunners and a serious rethink is required.
Southampton will be looking to pile on the misery in this midweek clash as they go in search of the win that would all but make certain of their Premier League safety.
The Saints board have been proved right in their decision to stick with Ralph Hasenhuttl earlier in the campaign when things looked bleak, with Friday's 3-0 victory against Norwich moving them 10 points clear of the dropzone.
With games against the likes of Watford, Everton, Brighton and Bournemouth to come in their remaining eight fixtures, Hasenhuttl's men can surely start preparing for the 2020-21 campaign.
Ending this season on a high will be the immediate aim for the Saints, of course, and they tend to do well in this fixture, winning three of the last five league encounters.
While the South Coast side have little left to play for on the face of it, Arsenal are in desperate need of victory to close the four-point gap on Sheffield United in seventh.
The Gabon striker, incidentally, has scored 49 Premier League goals, and one more here will see him become the sixth-fastest player to reach 50 in the competition (78 games).
Southampton's Premier League form: LLWLLW
Southampton's form (all competitions): LLWLLW
Arsenal's Premier League form: DWWWLL
Arsenal's form (all competitions): WLWWLL
If losing back-to-back matches since the restart was not bad enough for Arteta, the Spaniard has also lost three players to potential long-term injuries.
Matteo Guendouzi did at least escape retrospective action for grabbing Maupay by the throat last time out and is therefore expected to start in a depleted central midfield, which may include Mesut Ozil for the first time since early March.
As for Southampton, they remain without Moussa Djenepo following his dismissal against Newcastle United prior to March's lockdown.
Hasenhuttl could stick with the same lineup from the well-earned win over Norwich given the six-day gap between matches.
What is almost certain is that Danny Ings will continue to lead the line, with the Englishman having scored three goals in his last two Premier League appearances against Arsenal.
Southampton possible starting lineup:
McCarthy; Valery, Stephens, Bednarek, Bertrand; Armstrong, Ward-Prowse, Hojbjerg, Redmond; Ings, Obafemi
Arsenal possible starting lineup:
Martinez; Bellerin, Mustafi, Holding, Tierney; Ceballos, Guendouzi, Saka; Pepe, Nketiah, Aubameyang
We say: Southampton 1-1 Arsenal
Southampton have lost more home games than any other side in the Premier League this season. On the back of a morale-boosting win over Norwich last time out, however, we are backing the Saints to make a bad week even worse for Arsenal by picking up their first draw of 2020.