Broja sustained an ankle injury in the Saints’ 2-2 draw with Burnley.
Broja was ineligible for Tuesday’s Carabao Cup game at parent club Chelsea but would not have played anyway as he picked up an ankle injury after scoring in the 2-2 draw with Burnley last week.
The Albania international has still not recovered so will not be available at Vicarage Road.
Saints boss Ralph Hasenhuttl said: “Broja is not available for the weekend because he has an ankle injury in the Burnley game after scoring the goal.
“He will miss this game for sure.”
James Ward-Prowse will be back after suspension, but a few players who featured in the penalty shoot-out defeat at Stamford Bridge have issues.
“The rest, so far Prowsey is back, from the game on Tuesday we have one or two players with a few problems, muscle problems, not that hard,” the Austrian added.
“We have a good selection to pick the right team. This is important to have because one thing for sure is we had a very intense game on Tuesday and we will have one on Saturday. We need fresh players but also ones full of self-confidence.”
Southampton make the trip to Vicarage Road to face a team who won 5-2 at Everton last week to give new boss Claudio Ranieri his first victory in charge.
After a harrowing first game against Liverpool, the Hornets may have turned a corner, but Hasenhuttl is only concerned about his side.
“It shows how strong the Premier League is,” he added. “You can never be sure about an opponent, as Watford showed last week.
“First game against Liverpool was not so good, but this is normal and when a new manager comes in they need time.
“They seem to find the turnaround. For us we should concentrate on what we want to do and our strength and go there with all the conviction we have shown on Tuesday, but it will be a tough game.”