Martin Hunter's side are reaching the business end of the season, with just five games left to play in the Elite Group stage including tonight's.
Southampton currently sit fourth in the Elite Group, with the top three sides progressing to the end-of-season knockout tournament that decides the overall champion of the Barclays U21 Premier League.
Victory over the Gunners this evening would lift Hunter's team into third spot ahead of next Tuesday's trip to second-placed Manchester United.
Saints will be seeking to make amends for their disappointing two-nil defeat to the Gunners at Underhill last month.
That was Arsenal's first victory in the Elite Group, and they have since continued to pick up points to climb to fourth in the table.
Hunter will, therefore, be fully aware that an away win this evening would see his side leapfrogged in the standings.
Thankfully the Silverlake Stadium is proving to be something of a fortress for Saints, who have won all three of the U21 Premier League games they have played there so far.
Their last game in Eastleigh took place last Friday, when a young side saw off their Wolves counterparts by two goals to nil.
With that performance in mind, tonight's team could well be unchanged from the one that picked up its third Elite Group victory on Good Friday.
Alberto Seidi is still out injured, while it is unlikely that Hunter will be able to call on any First Team players less than 48 hours before Mauricio Pochettino's team take on Reading on Saturday.
Paulo Gazzaniga should keep his place in goal, while striker Jake Sinclair will be looking to build on the brace that secured that win over Wolves.
The Gunners have called upon a number of players with senior experience in recent weeks, with the likes of Ignasi Miguel, Nico Yennaris, Francois Coquelin and Conor Henderson playing in their win over Manchester United two weeks ago.
Tonight's game kicks off at 7pm, with admission at the Silverlake Stadium priced at £5 for adults and £3 for concessions.