Saints full-back Ryan Bertrand will miss the season opener after he sustained a knee injury during pre-season, but there hasn’t yet to be confirmation on how many more games he will miss for the club.
Claude Puel favoured a midfield diamond formation during pre-season, and looks set to start Shane Long and new signing Nathan Redmond together in a two-man front line.
But the Frenchman must prove they can cope without the departed Sadio Mane and Graziano Pelle, who scored 29 Southampton goals combined last season but moved on in the summer.
Watford head coach Walter Mazzarri is set to be without new signings Brice Dja Djedje and Isaac Success, whereas Craig Cathcart is expected to be on the line-up sheet after returning from a back problem.
A level playing field in terms of managers, Mazzarri is Watford's seventh boss in five seasons but just like Puel - despite enormous experience elsewhere - he is new to the Premier League.
The Hornets have stuck to a 3-5-2 formation for the majority of pre-season but huge pressure rests on Odin Ighalo to regain the goal-scoring form that helped them so much last term.
Ighalo scored just two goals in his 18 Premier League appearances in 2016 after managing 13 league goals in his initial 19 games, helping Watford to temporarily hold a European spot before Christmas.
Southampton ar unbeaten in their last five meetings with Watford, with three wins and two draws.
Watford have failed to score in any of the last four league encounters with the Saints and only managed just one shot on target in last season’s two fixture between the two clubs.
In 2016, Saints earned 39 points - a tally that was beaten by only one other team, champions Leicester who picked up 42.
They also ended last season with four consecutive wins and lost just one game out of ten league game at their home ground of St Mary's, though it remains to be seen whether Puel can continue such form.
The Hornets avoided relegation last season, their first year back in the Premier League, notching up a club record of 45 points although their form dropped after the halfway mark.
They were seventh in the table before the turn of the year, but they were unable to repeat their form from the first half of the season repeat as they managed just four wins and 17 points from their last 21 games.