Last Saturday, Mikel Arteta's side faced defeat at St Mary's in an FA Cup fourth round tie, ending their hopes of retaining last season's glory.
Expected team rotation
In the FA Cup, the Gunners fielded a weaker side compared to Southampton's first team regulars. The resting of Kieran Tierney, Alex Lacazette, Thomas Partey and Bukayo Saka hugely affected Arsenal's performance.
The introduction of Tierney will bring the passion and drive that Arsenal missed last time out against the Saints. The Scotsman has become a fan favourite amongst Gooners due to his impressive displays at left back.
The full back has created the third amount of chances (20) from open play this season for defenders, and will surely assist Arsenal to defeat Ralph Hasenhüttl's side.
Wonder kid Saka was hugely missed on Saturday after coming off the bench for Gabriel Martinelli.
With four goals and three assists in all competitions, as well as providing his agility and quick thinking, the young Englishman will for sure be a first pick for the starting eleven this Tuesday.
Although a few of Arteta's main men were rested in the FA Cup fixture last Saturday, Pierre-Emerick Aubameyang missed traveling to the south coast due to personal issues.
The Gabonese international travelled back home due to the unknown problem, leaving fans in the dark whether their captain will return to the first team this Tuesday.
If not, the talented Brazilian Martinelli, could replace the Arsenal captain on the left hand side, to provide his pace and sharpness against Southampton.
Arsenal's leading goal scorer, Lacazette, will be in favour to lead the line on Tuesday. The French striker has really hit the ground running recently, claiming seven goals to his name in the league.
A Lacazette start over Eddie Nketiah will give the North London side a more experienced attacking threat, giving the Gunners a chance to net against the Saints.
Dealing with Southampton strengths
Arsenal's defeat to Southampton last Saturday was not all due to team changes. It was also due to Southampton's constant domination over the Gunners.
Arteta's side failed to make a significant chance against the Saints, as well as failing to keep Hasenhüttl's side away from Bernd Leno's net.
Former Spurs man, Kyle Walker-Peters, was a thorn in Arsenal's side throughout the 90 minutes. A cross from the defender forced an own goal from Gabriel, the only goal of the game. This was the first goal Arteta's side had conceded in 508 minutes of football.
Che Adams also had a terrific chance to bury the tie, but it was saved by the German goalkeeper. Adams' strike partner and Euro squad contender, Danny Ings, was also danger to Arsenal's backline, seeing his chance hit the post.
A return for Tierney, as well as a potential start for the Ghanaian Partey, could resolve these defensive issues.
The threat the Saints midfield and attack imposed could be isolated due to the involvement of Partey. This isolation was evident after the midfielder came on for the last 30 minutes on Saturday.
Although Southampton's attack was an issue for Arsenal, the South coast side's defence was a major factor for their FA Cup success.
Inspirational performances from Jan Bednarek and Jack Stephens, halted the Gunners' chances of grabbing an important equaliser. Fraser Forster also stood strong between the sticks, saving a huge chance from Nketiah.
The absence of Lacazette, 'Auba', and Emile Smith-Rowe were factors within Arsenal's chance creation and goal scoring. If the trio appear on Tuesday, they will definitely change Arsenal's fortune in front of goal, pulling the result in Arteta's favour.
A must needed three points
Tuesday night will for sure be a well battled and fought game, with both sides needing three points, to keep them in the upper half of the table.
A win for Arteta's side will propel them into a potential eighth place, four points off the top four. Aston Villa will be behind in ninth with three games in hand.
However, a victory for the Saints could move them into sixth, depending on goal difference.
Success for Arsenal will continue their unbeaten streak to six games, reviving their dreadful start to this year's Premier League campaign.