Southampton have been a thorn in the Gunners' side in recent years—Arsenal have failed to beat them in three of their last four encounters, and Saints emerged victorious when the pair last met in the League Cup in 2014, though Arsene Wenger's side did come out on top when they played in September.
Read on for a full preview of the match, complete with viewing information and team news:
Date: Wednesday, November 30
Time: 7:45 p.m. GMT/2:45 p.m. ET
Live Stream: beIN Sports Connect USA
According to James Benge of the Evening Standard, Arsenal will continue to be without Hector Bellerin and Santi Cazorla, while Olivier Giroud, Mathieu Debuchy and Theo Walcott all picked up knocks on Sunday.
Indeed, the French pair both suffered hamstring injuries with Debuchy describing his as a "severe one," though Walcott could just be a doubt for the game. Meanwhile, Lucas Perez could be involved after returning to training on Friday, recovering ahead of schedule after suffering an ankle injury.
As for Southampton, Benge reported Sofiane Boufal and Steven Davis are set to return after missing Sunday's game through illness, but Dusan Tadic and Alex McCarthy are doubtful to play.
Predicted Arsenal Lineup: Emiliano Martinez; Carl Jenkinson, Rob Holding, Gabriel Paulista, Kieran Gibbs; Mohamed Elneny, Aaron Ramsey; Alex Oxlade-Chamberlain, Alex Iwobi, Jeff Reine-Adelaide; Lucas Perez
Predicted Southampton Lineup: Fraser Forster; Maya Yoshida, Jose Fonte, Cuco Martina, Sam McQueen; James Ward-Prowse, Pierre-Emile Hojbjerg, Sofiane Boufal, Josh Sims; Jay Rodriguez, Charlie Austin
After three draws in succession to kick off November—often the period during which Arsenal's season tends to falter—it appeared the Gunners had once again suffered a similar fate as they saw the likes of Chelsea and Manchester City surpass them in the Premier League and Paris Saint-Germain put themselves in pole position to top their UEFA Champions League group.
The Gunners bounced back from the run of stalemates with a 3-1 win at home to Bournemouth on Sunday, and it seems a little too much has been made from their brief winless run when put in the context of their entire season:
They'll be hoping to make the final four of the EFL Cup when they host Southampton and Claude Puel's side face the task of inflicting their first defeat in all competitions since the opening day of the campaign.
What will give them encouragement is their defensive record—they have shipped just 12 goals in the Premier League, bettered only by Chelsea and Tottenham Hotspur—and Arsenal's struggles to hit the target in recent games, per Opta's Orbinho:
While they have been clinical in the instances they have found the target, they were either own goals or scored by Alexis Sanchez, Olivier Giroud or Theo Walcott—potentially none of whom will be starting on Wednesday.
If the Gunners do end up relying on Alex Iwobi or Lucas Perez—who is a more than capable striker but has been out of action for some time—they might struggle to score.
Southampton aren't especially prolific themselves—only Burnley, Middlesbrough, Hull City and Swansea City have scored fewer than their 12 this season—but with Boufal likely to rejoin a strong attacking selection, Saints will be a threat.
Josh Sims may also keep his spot after providing an assist on his senior debut against Everton on Sunday. Per BBC Sport, the 19-year-old was thoroughly impressive:
Match of the Day host Gary Lineker also hailed the winger's performance:
The pacey youngster caused the Toffees no end of problems, and his fearless efforts could see him given the chance to test himself at the Emirates against an Arsenal back line unlikely to be composed of their regular starters.
It's set to be an intriguing showdown on Wednesday. Arsenal have the opportunity to dispel any further talk of their November struggles and of course edge closer to more silverware.
Likewise, Southampton will relish the possibility of reaching the semi-finals, arguably having the psychological edge after several positive results against the Gunners in recent years, and seem likely to put out a lineup to give themselves a strong chance of progressing—it could well be a hard-fought contest.