Real will play a Valencia side who have done much rebuilding this summer, with their six new signings including two midfielders, Sergio Canales and Fernando Gago, who have arrived from the Bernabeu.
Valencia finished third last season, but were 30 points adrift of Barcelona.
Barcelona begin life in the post-Pep Guardiola age with new manager Tito Vilanova taking charge of his first league game against Real Sociedad on Sunday as well. But there have been few other changes at the club, with Jordi Alba the only high profile signing.
On Sunday they will take on a Real Sociedad team who finished six points from relegation last season but were among several clubs to take a point off Barcelona in the early stages of the campaign, a run Guardiola’s team never recovered from as they tried to catch Madrid.
The action begins on Saturday with a match between newly-promoted Celta Vigo and a Malagateam who finished fourth last season but are now downgrading expectations after the scaling back of Sheikh Al Thani’s spending and the departure of Santi Cazorla to Arsenal.
Sevilla tackle Getafe and Real Mallorca host Espanyol in Saturday’s other matches.
Copa del Rey holders Athletic Bilbao face Real Betis on Sunday before two Europa League-bound teams, Levante and Atletico Madrid, face off.
The two other promoted teams, Deportivo La Coruna and Valladolid, must wait until Monday to get their campaigns started. Deportivo host Osasuna while Valladolid travel to Real Zaragoza while Rayo Vallecano host Granada, also on Monday.