Defending champions
Barca had to finish last season without the little Argentinian, due to a hamstring injury, and may have to do without him again Sunday at home to Levante.
Messi is suffering from a pulled muscle in his left leg, which forced him to miss Argentina's 2-1 defeat of Italy on Wednesday.
Levante's goalkeeper Keylor Navas said: "Things might be easier for us if Messi does not play. He is the best player in the world, without a doubt.
"Going to Barcelona is always difficult. Let's hope that they have still not picked up their usual rhythm."
If Messi is not fit then the Barca attack will be led by newcomer Neymar, who played the whole 90 minutes of Wednesday's Switzerland-Brazil friendly.
Barca may also be without Cesc Fabregas, who twisted his right ankle on the tour of Asia.
Later on Sunday, Real Madrid will kick off at home to Real Betis.
The whites will be sweating on the fitness of anchorman Xabi Alonso, who has been out since May with a groin strain. Also injured is newcomer Asier Illaramendi.
Youngsters Dani Carvajal, Casemiro and Isco will make their debuts for Real.
Meanwhile, Betis will be without injured veteran forward Ruben Castro, their main source of goals last season.
Betis coach Pepe Mel said: "When you go to the Estadio Bernabeu, you know that the whites are favourites. It will be very difficult to surprise them."
Also on Sunday, Osasuna will face Granada and Sevilla will take on Atletico Madrid.
Sevilla will be without Jesus Navas and Alvaro Negredo - both sold to Manchester City - while Atletico will be without Radamel Falcao, now at AS Monaco.
Leading the Atletico attack will be veteran David Villa, who was surplus to requirements at Barcelona. He will be alongside Brazil striker Diego Costa, who extended his contract at Atletico until 2018 on Thursday.
The Liga program will kick off on Saturday with Real Sociedad at home to Getafe, Valencia against Malaga and Valladolid against Athletic Bilbao.
Valencia's new coach Miroslav Djukic will have to decide between veteran Helder Postiga and teenager Paco Alcacer at centre-forward.
Monday will see Celta Vigo against Espanyol, Rayo Vallecano against Elche and, in a clash of promoted teams, Almeria against Villarreal.
