Spain centre backs Carles Puyol (knee) and Gerard Pique (foot) are both sidelined by injury, meaning Vilanova may have to start two of Sergio Busquets, Alex Song and Javier Mascherano – all midfielders by trade – in the heart of his defence.
Vilanova could also throw midfielders youngsters Marc Bartra or Andreu Fontas into the fray.
Barca's World Player of the Year Lionel Messi has fond memories of Granada having netted a hat-trick against the Andalusians last season that made him the club's record scorer on 234 goals in all competitions.
The Argentina forward has since netted 29 more, 19 at the end of last term and 10 this season in only seven appearances, including two in Wednesday's 3-2 Champions League comeback win at home to Spartak Moscow.
