A second-string Barcelona side were beaten 2-0 at Deportivo Coruna in the Primera Liga on Saturday.
Coach Frank Rijkaard was clearly focused on next week's Champions League semi-final second leg against Manchester United, retaining only three starters from Wednesday's 0-0 first-leg draw.
Juan Rodriguez and Pablo Amo took advantage of sloppy marking to put Depor in front in the second half as Barca effectively bowed out of the title race. The Catalans stay third on 61 points, one behind Villarreal who visit Real Betis on Sunday, and 11 adrift of leaders Real Madrid.
If Villarreal fail to beat Betis and Real win at home to Athletic Bilbao in Sunday's late game, Bernd Schuster's side will retain their league crown with four matches left to play.
Depor's sixth win in seven put them seventh, three points behind Sevilla, who missed out on a chance to close in on the Champions League places with a 0-0 draw at relegation-threatened Real Murcia in the late game.
Rijkaard had left Lionel Messi, Xavi and Samuel Eto'o out of the squad, and with Gabriel Milito and Andres Iniesta suspended, it was an unfamiliar line up who started in La Coruna.
The visitors dominated possession without managing to open up the massed home defence in the first half, and it was Depor who had the first clear sight of goal when reserve goalkeeper Jose Manuel Pinto fumbled a cross.
In the scramble that followed, Xisco lashed a shot against the bar and Rodriguez fluffed a shot wide of the post with the goal gaping.
Teenage striker Bojan Krkic provided Barca's greatest threat with a couple efforts, but Rodriguez made amends for his earlier howler, slotting home Angel Lafita's pull back from the touchline just after the break.
The home side took control of the game and defender Amo was left unmarked at the back post to nod in a free kick as Barca made it one win from nine in the league.