Mikel Arteta has been compared to Manchester United great Alex Ferguson after the number of international withdrawals the Gunners had in March.
But several genuine concerns perhaps mean Tonda Eckert's in-form Saints side have more of a chance than the bookies are currently giving them.
Saints host the top-flight leaders and Carabao Cup beaten finalists, who are still eyeing up a famous treble this season, at 8pm on Saturday, April 4.
The FA Cup, while Arsenal have not won a trophy since 2020, is clearly the lowest priority for Arteta, after the Premier League and Champions League.
Arsenal manager Mikel Arteta during a training session at the Sobha Realty Training Centre, London Colney. Picture date: Monday March 16, 2026. PA Photo. Photo credit should read: Bradley Collyer/PA Wire. RESTRICTIONS: Use subject to restrictions. Editorial use only, no commercial use without prior consent from rights holder.Arsenal boss Mikel Arteta will have an eye on Champions League (Image: PA)
Arteta will rotate as Arsenal face a demanding stretch of games with a Champions League quarter-final first leg against Sporting on Tuesday.
Then it's a Premier League clash with AFC Bournemouth, the European second leg and a potential title decider away at Man City by April 19.
Noni Madueke, Ebere Eze, Martin Odegaard and Martin Zubimendi are likely or definitely out with issues, while many others withdrew for fitness reasons.
These include the likes of stars Declan Rice, Bukayo Saka, Piero Hincapie, Leandro Trossard, William Saliba, Gabriel Magalhaes and Jurrien Timber.
Arsenal's Declan Rice during a training session at the Sobha Realty Training Centre, London Colney. Picture date: Monday March 16, 2026. PA Photo. Photo credit should read: Bradley Collyer/PA Wire. RESTRICTIONS: Use subject to restrictions. Editorial use only, no commercial use without prior consent from rights holder.Declan Rice is a doubt after withdrawing from England (Image: PA)
It means there will be a start for the exciting 16 year old England youth starlet Max Dowman, and maybe even 16 year old defender Marli Salmon.
Kepa Arrizabalaga has started in goal in cup competitions, while Christian Norgaard, Gabriel Jesus and Gabriel Martinelli have played every round so far.
Ben White and Myles Lewis-Skelly have featured prominently, while their versatility means they likely start at St Mary's, and Kai Havertz is back fit.
Arteta has the option to name Viktor Gyokeres, but he had a busy week with two World Cup play-offs. Italian defender Ricardo Califiori is the same.
But if Arteta feels one of rock-solid Saliba or Gabriel can play this game, as well as Rice in midfield, then the Arsenal team suddenly looks strong.
Possible Arsenal XI
(4-2-3-1): Kepa; White, Saliba, Mosquera, Lewis-Skelly; Norgaard, Rice; Dowman, Havertz, Martinelli; Jesus.