Lewandowski was Barca's top scorer last season and already has five league goals this campaign.
Yet the Pole was on the receiving end of a crunching tackle from Porto's David Carmo in Wednesday's 1-0 Champions League win and the Catalan club confirmed on Thursday that he would be out of action with no timeline for his return.
Barcelona, who trail Real Madrid by a point at the La Liga summit, also have to cope with injuries to Frenkie De Jong, Pedri and Raphinha.
Fortunately for Xavi, Granada, are second from bottom in the league with one win in eight games.
Xavi could turn to Lamine Yamal (16), who has already played 10 matches in all competitions this season, to complete the front three, along with Ferran Torres and Joao Felix, but will not want to risk overburdening the youngster.
Yamal made history as the youngest-ever starter in a Champions League match on Wednesday before being substituted late in the game.
While Barca's main goalscorer is on the sidelines, Real's seems to be in unstoppable form with midfielder Jude Bellingham (20) having scored eight goals in nine matches so far this season.
The Englishman was again on target when Real fought back to secure a barnstorming 3-2 win at Napoli in their Champions League clash on Tuesday.
Real will host 10th-placed Osasuna, who have won one of their last five league matches, on Saturday.
On Sunday, Real Sociedad travel to the defensively resilient Atletico Madrid, who have conceded seven goals this season, the joint second-fewest in the league, behind city rivals Real.
Sociedad's Takefusa Kubo will look to continue his rich form, with the Japanese player scoring five league goals this season, second only to Bellingham in the scoring charts.
Atletico are fourth with 16 points and Sociedad are a point behind.
Girona, the surprise package of the season so far, are third and two points behind Real. They travel to Cadiz on Saturday.
