All eyes will be looking to see how Setien will change Valverde's game plan and how he will be able to get the best out of Antoine Griezmann, especially with Luis Suarez, who has been so influential in recent weeks, now sidelined for several months after a knee operation.
Granada inflicted a shock 2-0 defeat at home to Barca earlier in the campaign, but have lost gas in recent week and Barca fans will want to see renewed vigor from their side as well as the defensive stability that has been missing for most of this season.
Atletico Madrid have to pick themselves up after the disappointment of another defeat on penalties to Real Madrid and make the difficult trip to play Eibar.
Atletico are still without Diego Costa, while Koke and Jose Gimenez are also injury victims of the Supercup, although Eibar also have injury worries of their own.
What promises to be a close game between mid-table Osasuna and Valladolid is played on Saturday evening with the home side looking to once again make their El Sadar stadium the fortress they need if they are to avoid struggling in the second half of the season.
An improving Valencia fly to struggling Mallorca to get the ball rolling on Sunday lunchtime as Albert Celades's side (who looked unmotivated in the Supercup) aims to maintain their rise up the table.
Real Sociedad travel to Betis for what should be an entertaining match between two sides that like to attack, while Raul de Tomas will make his league debut for bottom of the table Espanyol when they visit Villarreal.
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2020-09-15
2020-09-15
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2020-09-15