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Jurgen Klopp's side will be looking to build on their last-gasp victory over Tottenham on Sunday as they travel to the south coast to face the Saints.
With City winning against Cardiff on Wednesday, the onus is back on Liverpool to secure a valuable three points which would see see them go back to the top of the Premier League.
Southampton, on the other hand, sit five points above the relegation zone and are fighting for survival.
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Klopp warned his side to not underestimate the hosts, insisting Ralph Hasenhuttl has made Saints a tricky proposition, despite their league position perhaps not reflecting their true performance.
Kick-off is at 8.00pm from St. Mary's, with teams announced an hour before. Keep an eye out on LFC Globe for the latest alongside our live match-day coverage.