Three-time champions Inter Milan face a battle to get through Europa League Group K after a second successive defeat.
Atletico Madrid edged out Deportivo with a 1-0 victory and Valencia came from behind to beat Leganes 2-1 in La Liga.
Real Madrid failed in their bid to win a record 17th straight La Liga game as they were held 1-1 by Villarreal at the Bernabeu.
Villarreal captain Bruno Soriano kept his cool to score a Panenka penalty at the Bernabeu against Real Madrid on Wednesday.
Zinedine Zidane criticised Real Madrid's first-half performance after they were held to a 1-1 draw at home by Villarreal.
Scroll down to read all the action as Real Madrid are held 1-1 by Villarreal at the Bernabeu.
Guillem Balague discusses Barcelona's new system and Zinedine Zidane's decision to rest Cristiano Ronaldo and Gareth Bale.
Cristiano Ronaldo and Gareth Bale have returned to training ahead of Real Madrid's La Liga clash at home to Villarreal on Wednesday.
Villarreal forward Nicola Sansone scored a stunning long-range strike during his side's 2-1 win over Real Sociedad.
Jon Driscoll and Terry Gibson return for an in-depth take on all the action and major talking points in La Liga.
Villarreal secured a third consecutive win thanks to a goal of the season contender from Nicola Sansone in a 2-1 success at home to Real Sociedad.
Antoine Griezmann scored twice as Atletico Madrid won 4-0 at Celta Vigo in La Liga on Saturday, while Sevilla and Villarreal also claimed victories.
Sevilla and Villarreal played out a goalless draw on Sunday, while Las Palmas hit five past Granada to go top of the La Liga table.
Man Utd will face Fenerbahce, Feyenoord and Zorya Luhansk in the Europa League, while Southampton are in a group with Inter Milan.
Roma had two players sent off, lost 3-0 at home to Porto and missed out on the Champions League group stage on Tuesday night.
Sevilla twice recovered from going a goal down to secure a 6-4 home defeat of Espanyol in coach Jorge Sampaoli's first league fixture in charge.
The 21st season of live Spanish football on Sky Sports gets underway this weekend with over 300 games available throughout the campaign.
Transfer sagas, managerial changes, new faces, old problems - Guillem Balague previews the new La Liga season.
Ahead of the new La Liga season, Guillem Balague picks out five up-and-coming players to keep an eye on in Spain.
Dundalk's dreams of the Champions League group stages were left hanging by a thread after a 2-0 defeat by Legia Warsaw.