The Blaugrana leave out three Spain internationals for their Liga trip to the New Los Carmenes stadium this evening, with one eye on their upcoming European fixture against Milan
The Catalan side face AC Milan in the first leg of their last-16 clash at San Siro on Wednesday.
Javier Mascherano replaces Puyol at centre-back, while Adriano slots in at left-back and Alexis Sanchez starts alongside Lionel Messi and Pedro in an attacking three.
Xavi and David Villa miss this game due to injuries, with the latter admitted to hospital earlier this week because of kidney pains.
Granada name an unchanged team from the group that beat Deportivo La Coruna 3-1 on February 9, with Fran Rico and Dani Benitez still unavailable because of injuries.
Odion Ighalo leads the home side in attack as they try and make it three wins from three under new coach Lucas Alcaraz.
Granada (4-2-3-1): Tono; Nyom, Inigo Lopez, Mainz, Siqueira; Recio, Rico; Torje, Aranda, Nolito; Ighalo
Subs: To follow
Barcelona (4-3-3): Valdes; Alves, Pique, Mascherano, Adriano; Thiago, Busquets, Cesc; Alexis, Messi, Pedro
Subs: Pinto, Montoya, Puyol, Alba, Song, Iniesta, Tello