Watford will look to bounce back from Thursday's defeat at Burnley, and a home win would take them four points clear of the relegation zone.
Southampton, lying 14th, are targeting back-to-back away wins and a first league double over Watford since the 2011/12 Championship campaign.
Watford report no new injury concerns ahead of Sunday's match but head coach Nigel Pearson has confirmed that he will look to rotate his squad.
Only Gerard Deulofeu (cruciate ligament), Daryl Janmaat (knee) and Isaac Success (Achilles) remain unavailable for the Hornets.
Southampton will assess midfielders Pierre-Emile Højbjerg (thigh) and Sofiane Boufal (ankle), while Jack Stephens and Moussa Djenepo are suspended.
Watford have won four of their last seven Premier League home matches (D2 L1), including victories over Manchester United and Liverpool. They had previously gone 12 consecutive top-flight outings without a win at Vicarage Road.
Ben Foster can become only the 19th player to start 100 consecutive Premier League matches and, aged 37 years and 86 days, the oldest player to reach the century.
Southampton have won a league-high 62 per cent of their Premier League points on the road in 2019/20, with 23 out of 37.
In last season's corresponding fixture, Southampton's Shane Long scored the fastest ever goal in Premier League history, finding the net after just 7.69 seconds.
Referee: Michael Oliver. Assistants: Stuart Burt, Daniel Cook. Fourth official: Kevin Friend. Replacement official: Daniel Leach. VAR: Chris Kavanagh. Assistant VAR: Sian Massey-Ellis.