It means plenty of changes are expected from Jurgen Klopp to keep his squad fresh after being handed a fair warning for potential injuries at Wembley.
But victory remains firmly at the top of the priority list to ensure the Premier League title race goes to the final day.
After Man City dropped points at West Ham, a win for Liverpool tonight keeps the Reds in the hunt at Anfield on Sunday, while Steven Gerrard takes his Aston Villa side to the Etihad.
So, can the Reds ensure this one goes the distance?
Check This Is Anfield for the latest team news ahead of the match.
You can also follow the game by downloading the This is Anfield app, including lineups, live coverage and all the reaction and analysis.
The match gets underway at 7.45pm (BST) – or 2.45pm in New York, 11.45am in Los Angeles, 4.45am (Wednesday) in Sydney, 10.45pm in Dubai and 9.45pm in Nairobi.
UK Viewers
Southampton vs. Liverpool is being shown live on Sky Sports Main Event and Sky Sports Premier League in the UK, which are available to live stream with Sky GO.
This Is Anfield will also be providing live text commentary throughout on our website and full match reaction and analysis on the This Is Anfield app for iPhone and Android later.
US Viewers
Southampton vs. Liverpool is being shown live on the USA Network and NBC Universo in the US, which are available to live stream with FuboTV here.
This Is Anfield will also be providing live text commentary throughout on our website and full match reaction and analysis on the This Is Anfield app for iPhone and Android later.
Worldwide
Live audio commentary of Southampton vs. Liverpool and a full match replay and highlights will also be available on LFCTV GO here.
Check our Rest of the World TV guide below for a list of TV broadcasters showing the match live.
This Is Anfield will also be providing live text commentary throughout on our website and full match reaction and analysis on the This Is Anfield app for iPhone and Android later.
