Saints boss Mauricio Pellegrino is under pressure to turn the club's fortunes around after a difficult start to the season.
Southampton are 17th in the table and only goal difference is keeping them out of the bottom three after the first 22 Premier League games.
Pellegrino's men last won in November against Everton but they showed their class in the FA Cup third round tie against Fulham last week.
While forward Charlie Austin remains on the sidelines with a hamstring injury, defenders Wesley Hoedt, Cedric Soares and Jeremy Pied have all returned to training.
Like Southampton, Watford have struggled of late and they have won one of their last nine league games. That form has seen Marco Silva's men drop down to 10th but he will be boosted by the return of captain Troy Deeney.
Deeney is back after serving a four-match ban but Younes Kaboul, Craig Cathcart, Isaac Success, Miguel Britos, Kiko Femenia, Will Hughes and Nathaniel Chalobah all remain on the sidelines.
Watford's only win in the last eight top-flight home matches against Southampton came in December 1999 and they will need to dig deep to get the job done on home soil.