The Hornets announced earlier this week that Mazzarri would leave his role as manager at the end of the season.
The Italian only took over the reins at Vicarage Road last summer and despite preserving the club's Premier League status, it has now been confirmed that he will leave for pastures new.
Mazzarri faces something of a defensive crisis heading into the match, as Sebastian Prodl is suspended following his sending off against Chelsea last time out, while fellow centre backs Christian Kabasele and Miguel Britos are struggling with respective hamstring and calf complaints.
Manchester City need just a point to be assured of a top-four finish, while a victory will guarantee them third place and with it, an automatic route into next season's Champions League group stage.
The Citizens are unbeaten in their previous seven league games, winning the last three, while they are also unbeaten in their last ten matches against Watford.
John Stones appears to have recovered from a groin strain and could be handed his first start in over a month after featuring as late substitute during the midweek victory over West Brom.
Vincent Kompany, the man Stones replaced during that contest, is also expected to be fit despite his late withdrawal at the Etihad Stadium, while Pablo Zabaleta could feature for the final time as a City player.
City secured a 2-0 victory when the two teams met at the Etihad Stadium earlier in the season, with Zabaleta and David Silva grabbing the goals.