Both these sides will be looking to boost their positions in the Premier League table after both came away from their matches before international break with 0-0 draws.
Marco Silva's Watford will be after the Portuguese first back-to-back away victories for the first time in his managerial career. The Saints sit with an impressive record against Watford with the home side unbeaten against their opposition in their last five meetings - three wins and two draws in the Saints favour.
Both teams will be looking to build on last seasons outings with new management at the helm after finishing with only six points separating the two lasts season, despite Saints finishing 8th and the Hornets 17th.
You only have to look back as far as 4th March this year, an encounter which provided an abundance of goals from both sides with control of the game swaying between one side and the other.
The league match, at Vicarage Road, saw Watford go ahead early on with a goal from Troy Deeney on 4 minutes. Goals from Dusan Tadic and Nathan Redmond - who has been involved in five goals against Watford in his last three appearances against them - saw the visitors lead 2-1 at the interval.
Four goals in a frantic last 11 minutes saw Watford battle back to two-all through Stefano Okaka, only to concede two in quick succession from Manolo Gabbiadini and Redmond once more to wrap up the match.
However Abdoulaye Doucoure grabbed a 90th minute goal for the Hornets as the visitors had a nervy finish to the match, Southampton holding on to the 4-3 win in the end.
Nathan Redmond vs Daryl Janmaat
With the Dutchman only making his return from injury he'll be facing a difficult task against Watford's bogey man in Redmond who seems to find his way to the net against this opposition.
The 23-year-old winger's pace and flair for the Saints will certainly prove troubling for a patched together Hornets defence with a number of first team regulars at the back missing.
Keeping Redmond's influence in the final third to a minimum will be crucial to Watford success away from home, with Janmaat needing to be focused on marshalling the England man out of the contest.
Saints fans will be boosted by the news that star man Virgil van Dijk has been back in first team training this week and will see his return to action soon.
Mauricio Pellegrino has the fortunate news of no fresh injuries to worry about and a first team squad at full strength.
However Watford manager Silva will have a headache when it comes to his sides' defence with Miguel Britos suspended after his foul on Anthony Knockhaert in their Brighton game.
Fellow defenders Craig Cathcart (knee) and Sebastian Prodl (knock) are set to miss out.
Good news for the Hornets sees the potential returns of midfielder Roberto Pereyra with Daryl Janmaat and Younes Kaboul fit, meanwhile new signing Andre Carillo - signed from Sporting Lisbon - should be set to make his first start for the club.
Potential Southampton Starting Lineup: Forster, Cedric, Stephens, Yoshida, Bertrand, Romeu, Lemina, Redmond, Davies, Tadic, Gabbiadini
Potential Watford Starting Lineup: Gomes, Kiko, Mariappa, Kabasele, Janmaat, Doucoure, Pereyra, Chalobah, Carillo, Richarlison, Gray
With the Saints solid record against Watford it could be easy to see another Redmond show at St. Mary's on Saturday but Marco Silva has drilled his side well and got them playing solid football compared to last year.
With to sides searching for a strong mid-table finish it is difficult to see one clear victor from the meeting. However Southampton's strength and the form of Redmond and Gabbiadini should see the Saints see off their competition in this meeting.
And with goals guaranteed between these sides it should live up to the billing.
Prediction: Southampton 3-1 Watford