With Luis Suarez limping off in the same game with a calf injury and it revealed on Monday that Ousmane Dembele is set for five weeks on the sidelines with a hamstring problem , it seemed all of the attacking responsibilities would be heaped on the shoulders of summer signing Antoine Griezmann.
However, Barcelona have been handed a major boost with Goal learning that Messi is now ready to be included in Ernesto Valverde's plans.
The 32-year-old picked up a calf injury early in his pre-season preparations having returned from Copa America duty, and has been training away from the main group.
He is now back in full training, though, as the Blaugrana look to get their first points on the board.
Messi is expected to be named in the matchday squad, and it is likely he will feature from the bench.
A double session has been scheduled for the diminutive frontman during the week, taking his tally to five training sessions ahead of Sunday's clash.
Messi's return should ease the load on Griezmann, whose task in forward areas looked to have been made even more difficult following the completion of Philippe Coutinho's loan move to Bayern Munich .
Valverde demanded more from France international Griezmann in the aftermath of the defeat to Athletic, insisting: “If he is close to the box he can finish, he moves well, but you have to dominate the game for that to happen.
“Putting him on the left, we knew that he will look for goal, but we have a left-back and players who can take the game.
“(However), we expect a lot from all the players and he has to look to get in the game more.”
While Barca host Betis, Real welcome Real Valldolid to Santiago Bernabeu on Saturday and Atletico go to Leganes the following day.