The Argentine superstar picked up a knock in the win against Granada and has missed full training in the days since.
Messi featuring for Barca, though possible, is highly unlikely as head coach Ronald Koeman will be keen to avoid making any injury worse.
Therefore, expect Martin Braithwaite to come into the starting XI for the game against the Basque side.
It will, naturally, be a blow to miss Messi, especially in the kind of form he is in at the moment.
He put in a sparkling performance at the weekend, scoring two lovely goals in the aforementioned win versus Granada.
The Frenchman enjoyed one of his best performances of the season, scoring two goals and recording an assist to earn a 9.6 FC Rating.
Expect Griezmann and Ousmane Dembele to play either side of Braithwaite in a front three.
There could be a change further back, with Koeman potentially giving some minutes to Miralem Pjanic in the three-man midfield alongside Frenkie de Jong and Pedri, with Sergio Busquets rested to the bench.
Clement Lenglet was suspended for La Liga duties, but is now available and should be placed right back in to the starting XI.
Gerard Pique, Philippe Coutinho, Sergi Roberto and Ansu Fati are all long-term absentees.