Arsenal go into the match on the back of a thumping 4-1 win over CSKA Moscow on Thursday.
But despite the convincing win, Arsenal boss Arsene Wenger may opt to rest some of his big names.
For Southampton, they start the match three points from safety and in the relegation zone.
But a win will take the Saints out the bottom three with six games to play.
In the fixture between the two sides in December, Olivier Giroud scored a late equaliser to rescue a point.
Arsenal vs Southampton start time
The match kicks off at 2.15pm.
Where is Arsenal vs Southampton being played?
The match is being played at the Emirates Stadium.
How to watch Arsenal vs Southampton on TV
The game is being broadcast live on Sky Sports and is being shown on the Premier League and Main Event channels.
Coverage starts at 1.30pm.
Arsenal vs Southampton live stream
Sky subscribers can stream the match online via SkyGo and the SkyGo app.
This means that all the action can be followed on your desktop or laptop via the Sky Go app, which if you’re an existing customer, is also available on iOS and Android smartphone and tablet devices.
Sky Go is also available on a number of platforms including Amazon Fire devices, iPad, Mac computers and laptops, Playstation 3, PS4 and Xbox One.
The Sky Sports app, available to download on iOS and Android devices, will also be providing live text coverage and updates.
If you’re not currently a Sky Sports customer but can’t stand to miss out on the action, you can add the channels to your box via a NOW TV subscription.
Day passes, which let you add Sky Sports channels for 24 hours, start at £6.99 a day, with a weekly pass starting from £10.99, and no locking in to a contract.
NOW TV doesn’t even require a typical television to use, as it is also available on a NOW TV Box, Chromecast, PS4, PS3, Xbox One, Xbox 360, Roku, LG Smart TV, PC or Mac, and selected mobile and tablet devices.
Arsenal vs Southampton squads
Cech, Macey, Holding, Mustafi, Chambers, Bellerin, Koscielny, Mertesacker, Monreal, Nelson, Kolasinac, Maitland-Niles, Xhaka, Elneny, Wilshere, Ramsey, Ozil, Iwobi, Welbeck, Lacazette, Nketiah, Aubameyang.
Forster, McCarthy, Taylor, Soares, Pied, Bertrand, Stephens, Hoedt, Yoshida, Targett, Lemina, Davis, Romeu, Ward-Prowse, Hojbjerg, Boufal, Long, Redmond, Tadic, Gabbiadini, Austin, Carrillo.
Arsenal vs Southampton odds
Arsenal win 3/5
Southampton win 5/1