Emre Can could play his 100th game for the Reds in all competitions. After scoring twice in his first 62 Premier League games, the Germany international has found the net in his last two top-flight outings.
The Reds have lost just one of the last six meetings between the sides in all competitions.
In three games last season, Liverpool won one, drew one and lost one. The 6-1 League Cup victory at St Mary's last December represents their biggest ever win at Southampton.
Sadio Mane scored four of Southampton's five goals in those three games.