Karim Benzema (35) struck a hat-trick as Real won the semi-final second leg 4-0 at the Camp Nou to overturn a one-goal deficit and leave Barcelona, who were also eliminated from the Europa League in February, with just the league title to play for.
Top of the league on 71 points, 12 ahead of second-placed rivals Real with 11 games left, Barcelona's players must now ensure that it's plain sailing in the home stretch of the campaign as they edge closer to the club's 27th LaLiga title.
"We have lost 0-4 but we can win the league and the Super Cup, so we can have a very good season," Barca coach Xavi told reporters on Wednesday.
"We are already focused on the league, I have told the players: 'change your mind, think about Girona, rest...'.
"It is a tough night and it will be difficult for us to digest it, but I am thinking about Girona. We have to be positive."
Elsewhere, Real, who take on sixth-placed Villarreal, will look to continue their free-scoring form ahead of next week's Champions League quarter-final first leg against Premier League Chelsea.
Carlo Ancelotti's side will be boosted by striker Benzema's timely return to form, with the Frenchman having scored hat-tricks in his last two outings after failing to score in three straight league games.
However, Real would do well to be wary of Villarreal, who have won their last two league games and emerged victorious when the teams last met in LaLiga in January.
The two clubs and Espanyol are all tied on 27 points from 27 games, with Valencia in 17th thanks to their superior goal difference.
A defeat would see Valencia slip into the relegation zone and a step closer to spending their first season in the Spanish second tier since 1986-87.