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The French international midfielder, 28, was sidelined for all but the final match of last season with anterior cruciate ligament damage.
"He is a giant, mentally," said Wenger. "To do what he has done, coming back every time from the severe injuries he has had, deserves a lot of respect.
"He played 90 minutes for the under-21s last week and will play against Southampton."
Wenger is likely to rotate his squad and could give a debut to goalkeeper David Ospina, who has yet to feature since joining from Nice.
Tomas Rosicky, Joel Campbell and Lukas Podolski will also hope to start, but Mathieu Debuchy is out for three months after undergoing ankle surgery.
Youngsters Isaac Hayden, Chuba Akpom and Semi Ajayi may feature.
Southampton hope James Ward-Prowse and Maya Yoshida will be fit despite being forced off with injuries at Swansea.
Toby Alderweireld is likely to again miss out with a hamstring problem.
Forward Sadio Mane is set to make his first appearance since joining from Red Bull Salzburg.
Victory in last season's FA Cup final ended Arsenal's nine-year wait for silverware, but the League Cup is the one domestic trophy that has so far eluded Arsene Wenger in his 18-year tenure as Gunners boss.
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“It is nice for the fans and for everybody who loves the Saints - the start is fantastic for us”
Ronald Koeman Southampton manager
The Frenchman has rarely prioritised the competition, and despite reaching the final on two occasions, he has often chosen to blood youngsters in the early rounds.
However, Arsenal's recent recruitment, which has reportedly taken their wage bill above Chelsea's for the first time in more than a decade, means the Gunners have a raft of senior players in need of a run-out on Tuesday.
Ronald Koeman gained his first win as Southampton boss as Saints eliminated Millwall in the second round.
That victory has proved a catalyst for an encouraging run of form that has yielded three successive Premier League wins, taking Saints up to second in the table - their highest top-flight position since 1988.
A first victory at the Emirates would give them five consecutive wins in all competitions - which would be their best run for over three years.
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