Atletico Madrid suffered a shock from the Copa del Rey when Girona called for a 3: 3 draw in the first leg to beat the away winners in the final eight.
Atletico was the perfect start with the start of Nikola Kalinic.
Valery Fernandez and Cristhian Stuani drew the match against Girona before Angel Correa.
Antoine Griezmann's goal was to bring the hosts to the next round, but Seydou Doumbia scored two minutes before the final whistle for Girona.
There was further bad news for a team from Atletico, in which already some first-team regulars were absent due to injuries. Spanish midfielder Saul Niguez had to stop early in the second half due to a muscle problem.
In the other Copa del Rey last 16 legs on Wednesday, Leganes beat real Madrid 1: 0, although Real scored an overall advantage of 3: 1.
Martin Braithwaite, on loan from Middlesbrough to Leganes, scored the only goal of the match from close range after his earlier header hit the post.
Real, without the injured Karim Benzema and Gareth Bale and rested with Luka Modric and Sergio Ramos, keeper Keylor Navas needed a series of parades.
Seville, Third in the league, also reached the last eight and struck Athletic Bilbao A total of 3: 2, although he lost 1-0 in the second leg thanks to a goal from Gorka Guruzeta.