Atletico Madrid became the surprise table toppers on Sunday after beating Valencia 2-0 following a thrilling day of La Liga action which saw champions Barcelona lose 4-3 at Celta Vigo and Real Madrid held to a 1-1 draw at home to minnows Eibar.
Barca had the chance to go top after Real drew a fourth consecutive game in all competitions for the first time in over a decade but they were rattled by rampant Celta who capitalised on a litany of mistakes from Luis Enrique's side.
The Barca coach rotated his team after the hard-fought 2-1 win at Borussia Moenchengladbach in the Champions League on Wednesday, leaving experienced defender Javier Mascherano out and starting without midfield maestro Andres Iniesta.
His side paid dearly for the changes and fell behind to Pione Sisto's low strike in the 22nd minute after an uncharacteristic mistake by midfielder Sergio Busquets.
Iago Aspas finished off a quick counter to double the home side's advantage in the 31st and two minutes later Barca were hit again, Jeremy Mathieu bundling into his own net.
Iniesta came on at the start of the second half to mark his 600th appearance for Barca and nearly engineered a dramatic turnaround, assisting Gerard Pique's headed goal and helping to win a penalty which Neymar coolly converted.
Barca were quickly on the back foot again, however, following an embarrassing error by goalkeeper Marc-Andre ter Stegen, who kicked the ball against Pablo Hernandez and watched it go straight into the net in the 77th minute.
Pique reduced the deficit back to one goal in the 87th but they could not wipe out the damage done by their shaky defence.
"We have to pick ourselves up from this, it was not our best night," Luis Enrique told a news conference.
"We were inferior to our opponents, we did not start well and just as we got ourselves back into it we reverted to how we were at the start and they ran away with it. We've lost three vital points today."
Atletico have 15 points, ahead of Real on goal difference, while Barca are fourth on 13, one point behind Sevilla in third.
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