Vezo, who has featured in eight of Setubal's Primeira Liga matches this season, will move to the Spanish club in January, having agreed personal terms and undergone a medical.
Until then, he will continue to be available for selection at Setubal, with the Portuguese club having also secured a 25 per cent sell-on clause.
Vezo graduated through the youth setup at the Estadio do Bonfim before making his first-team debut in the season-opening defeat to league champions, Porto.
The Portugal Under-19 international could act as a replacement for defender Adil Rami, who will join Milan on loan in January after falling out of favour with head coach Miroslav Djukic and being placed under suspension by the Liga club.
When he arrives at the Mestalla, Vezo will link up with compatriots Joao Perreira, Ricardo Costa and Helder Postiga.
