Martin Odegaard is back for Arsenal
Arsenal Football Newsletter
The Gunners face the Championship side with a place in the semi-finals, and a swift return to Wembley, on the line.
Odegaard has not played since February 22 due to a knee injury but has overcome that and is selected to start at St Mary's.
Mikel Arteta confirmed that Jurrien Timber, who has missed the last two matches with a groin injury, could also be back. However, the Dutchman is not in the matchday squad.
Noni Madueke suffered an injury while on international duty with England, but the winger is not expected to face a significant spell on the sidelines and is on the bench.
“It looked really bad," Arteta said.
"Noni was really worried, especially after what happened in his other knee a few weeks out and he was out for six weeks. But no, it’s nowhere near that injury. That was really good news.”
Asked whether it could be a matter of days before Madueke is back, Arteta responded: "I think so."
Noni Madueke is on the bench
Eberechi Eze and Piero Hincapie have both also been ruled out of the Southampton match.
Arsenal had six other players withdraw from international duty, though most of those were related to managing ongoing issues rather than any significant setbacks.
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Arteta said only "let's see" when asked if any of those stars would be available, but the likes of Martin Zubimendi, Declan Rice and Bukayo Saka are all rested.
Dowman starts on the right wing in what is the 16-year-old's first appearance since he dragged Arsenal to victory off the bench against Everton.
There are rare minutes for Christian Norgaard and Gabriel Jesus, while Kepa Arrizabalaga keeps his place despite his major mistake in the Carabao Cup final defeat to Manchester City.
Confirmed team news
Arsenal XI: Arrizabalaga, White, Mosquera, Gabriel, Lewis-Skelly, Norgaard, Odegaard, Havertz, Dowman, Martinelli, Jesus
Substitutes: Raya, Saliba, Gyokeres, Madueke, Calafiori, Zubimendi, Harriman-Annous, O’Neill, Salmon