Barcelona, on top of the table with two wins, lead champions Real by five points after two matches.
A draw at home to Valencia and a loss away to Getafe has seen Real make their worst start to a season in 39 years.
Barcelona, on the other hand, thumped Real Sociedad at home before pinching an away win over Osasuna.
Real will take on Granada at the Bernabeu on Sunday, followed by Barcelona's clash against Valencia at Camp Nou.
Jose Mourinho's side will be buoyed by their Spanish Super Cup success over Barcelona midweek, while Granada, who narrowly avoided relegation last season, aim to somehow defy the odds.
Valencia will travel to Barcelona hopeful of securing at least a point at Camp Nou for the first time since 2008.
Mauricio Pellegrino's men have performed admirably against Barcelona in recent fixtures and are full of confidence after taking a point at the Bernabeu in their season opener.
In other matches, Celta de Vigo and Osasuna, who both lost their opening two fixtures, clash on Saturday.
Champions League qualifiers Malaga will travel to face Real Zaragoza, while Deportivo de La Coruna play Getafe at home.
Mallorca will attempt to continue their unbeaten start at home to Real Sociedad, while Levante meet Espanyol in Valencia.
Elsewhere on Sunday, Rayo Vallecano, one of three sides with six points, will take on Sevilla at home, while Athletic Club play host to Real Valladolid, who also boast a perfect record.
Real Betis and Atletico Madrid, fresh from their UEFA Super Cup outing against Chelsea, will play in Seville on Monday.