Both sides bounced back from disappointments in Europe to score important Premier League victories last Sunday, and will now want to build on their success by reaching the last four of the first cup competition of the season.
Far from an unimportant game
With both the Gunners and Saints being involved European competition this season and facing a typically hectic fixture list over Christmas and New Year, one may assume that the EFL Cup is not at the top of either sides' priorities.
Undoubtedly, they each have bigger fish to fry. Manager Arsene Wenger will be determined to recapture the Premier League title for Arsenal after well over a decade of near-misses and wondering what might have been. A deep run in the Champions League is also long overdue.
Likewise, Claude Puel's Southampton will already have one eye on their must-win Europa League encounter with Hapoel-Be'er Sheva next week, and their inconsistent domestic form also needs resolving.
However, continued progression in the EFL Cup could be crucial to Arsenal and Southampton's seasons. The competition gives players on the fringes of each squad vital minutes on the pitch, and winning games can only be a good thing for morale and team spirit.
It may not be the most important game of the campaign, but it is most certainly an opportunity, rather than a burden. With a tricky run of games coming up, both sides could do with a confidence-boosting victory or for a player who has been out of favour to suddenly prove his worth. This match provides the perfect setting for just this.
The importance of this match has been emphasised by both camps. Gunners goalkeeper Emiliano Martinez stated that "we want to go all the way", while Saints manager Puel has recognised the competition as "an opportunity to try and win something."
Arsenal defender Mathieu Debuchy sustained a hamstring injury during Sunday's victory over Bournemouth, meaning he is unavailable. Striker Lucas Perez could return for the hosts. Hector Bellerin, Danny Welbeck, Per Mertersacker and Santi Cazorla all remain unavailable.
As for Southampton, regular cup goalkeeper Alex McCarthy is out with a hamstring problem, meaning Puel could give debuts to either the young Harry Lewis or the veteran Stuart Taylor if he decides to rest number one Fraser Forster. Defender Matt Targett's return from his hamstring injury is still a few weeks away.
Match Facts and history
Arsenal have won the League Cup twice, Southampton none.
In the five League Cup ties between the teams, Arsenal have won all but one.
Southampton have lost their last seven League Cup quarter finals, while Arsenal have lost four of their last five.
Southampton's only ever victory at The Emirates came in the EFL Cup (then Capital One Cup), when they won 2-1 in September 2014.
Arsenal's Theo Walcott and Alex Oxlade-Chamberlain both began their professional careers at Southampton, while Stuart Taylor spent eight years with the Gunners.