The Gunners are in freefall down the league table, and there is massive pressure on manager Mikel Arteta to get things back on track.
Since beating Manchester United 1-0 at Old Trafford in early November, Arsenal have picked up one point in five Premier League games.
The Gunners have also lost their last four league games at the Emirates Stadium.
With London being placed back in tier 3 of the United Kingdom's COVID-19 restrictions, it means that no fans will be allowed into the stadium for this game.
Arsenal are in 15th place, just five points above the drop zone, which is a staggering drop in standards for the club. In their last match, they lost 1-0 to Burnley, who are one of the five teams below them in the standings, which was a massive cause for concern.
In contrast, fourth-placed Southampton are flying. With Liverpool and Tottenham facing each other on Wednesday, the Saints may have a chance to leapfrog one of them if they win this game.
Southampton condemned Sheffield United to yet more misery at the weekend, as they ran out 3-0 winners at St. Mary's in a game that they dominated from start to finish.
Arsenal vs Southampton Head-to-Head
This will be the 100th clash between Arsenal and Southampton, with the Gunners having won 51 of those. Southampton have won only 21 of those games, with 27 ending in draws.
Arsenal form guide: L-W-L-W-L
Southampton form guide: W-W-L-D-W
Arsenal vs Southampton Team News
Hector Bellerin and Granit Xhaka are both suspended for this game. Bellerin has picked up five yellow cards this season, while the Swiss international was sent off after grabbing Ashley Westwood by the neck in their loss to Burnley.
In good news for the Gunners, Nicholas Pepe will return from suspension.
Injured: Reiss Nelson, David Luiz, Thomas Partey, Sead Kolasinac
Suspended: Granit Xhaka, Hector Bellerin
The Saints have no known concerns in terms of injuries or niggles.
Arsenal vs Southampton Predicted XI
Arsenal Predicted XI (4-2-3-1): Bernd Leno; Cedric Soares, Rob Holding, Gabriel Magalhaes, Kieran Tierney; Dani Ceballos, Mohamed Elneny; Nicholas Pepe, Alexandre Lacazette, Bukayo Saka; Pierre-Emerick Aubameyang
Southampton Predicted XI (4-2-2-2): Alex McCarthy; Kyle Walker-Peters, Jan Bednarek, Jannik Vestergaard, Ryan Bertrand; Oriol Romeu, James Ward-Prowse; Stuart Armstrong, Nathan Redmond; Che Adams, Danny Ings
Arsenal vs Southampton Prediction
In the current form of these two teams, there is only one likely winner.
Southampton are playing vibrant attacking football, and that could prove too much to handle for an Arsenal defence that sometimes play as though they have never seen each other before.
Prediction: Arsenal 1-3 Southampton