The Blues beat the Terriers with ease on Tuesday, and without record signing Alvaro Morata, but remain 14 points off champions-elect Manchester City.
Southampton came within minutes of beating Arsenal at the weekend before shipping four goals at home to Leicester City. Who will turn up at Stamford Bridge on Saturday?
Chelsea welcome back top scorer Alvaro Morata, who missed the win at Huddersfield through a combination of fatigue and a back problem.Defender David Luiz is continuing his rehabilitation from inflammation on his knee and remains out.
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Chelsea have won each of their last three Premier League games against Southampton since losing 3-1 at Stamford Bridge in October 2015.
Saints have kept one clean sheet in their last 24 league games against the Blues – a goalless draw in west London on Boxing Day 2002.