The former Rubin Kazan boss was swiftly appointed as Marco Silva's successor after the 40-year-old Portuguese was sacked last Sunday, and he will hope to begin his reign at Vicarage Road with a win.
The Saints are fight for their Premier League place this season, but an FA Cup win against the Hornets would certainly provide a welcome boost in confidence for the side from St Mary's; a home win is chalked up as a 10/11 (1.91) chance with Paddy Power.
James Ward-Prowse scored twice for Southampton against the Hornets at Vicarage Road earlier this month and, having scored the winner against Fulham in the previous round of this competition, is likely to feature here.
Craig Cathcart, Kiko Femenia, Nathaniel Chalobah and Miguel Britos are all likely to be enforced absentees for the Hornets once again this weekend.
Both teams to score?
There have been goals at both ends in each of Southampton's last six home matches and Paddy Power offer 4/5 (1.80) that the trend continues here; the same firm offer even money (2.0) that there are more than two goals in the game.
Tips and predictions
Southampton have scored first in five of their last six matches on their own patch - with each of those coming inside the opening 25 minutes.
Paddy Power's 5/6 (1.83) quote, therefore, for the Saints to score before the break could represent good value for punters ahead of Saturday's showdown at St Mary's.