The England centre-back came on as a late substitute in the midweek Premier League win over West Brom after six games out with a groin injury.
Midfielders Fabian Delph (leg) and Ilkay Gundogan (knee), and goalkeeper Claudio Bravo (calf) are out while right-back Pablo Zabaleta makes his final appearance for the club.
There is also uncertainty over the futures of Yaya Toure, Jesus Navas, Willy Caballero, Bacary Sagna and Gael Clichy, who are all out of contract this summer.
Zabaleta was one of the scorers when his side beat the Hornets 2-0 in the reverse fixture back in December.
A repeat of that result will see Pep Guardiola's men finish third in the table and therefore qualify for the group stage next season's Champions League.
Provisional squad: Caballero, Gunn, Zabaleta, Sagna, Stones, Kompany, Otamendi, Clichy, Kolarov, Toure, Fernando, Fernandinho, De Bruyne, Sane, Sterling, Nolito, Navas, Silva, Aguero, Jesus, Iheanacho.