Valencia claimed a well-deserved 3-2 win at the Camp Nou Stadium, which was the first big upset of the Spanish league season.
Goals from Dani Parejo, Pablo Piatti and Juan Alcazar gave Valencia three important points and ended Barca's 100 home record, Xinhua reported Saturday.
Just as importantly the defeat means that should Atletico Madrid draw or Real Madrid win their games Sunday they will knock Barca off the top of the table for the first time in 60 weeks
Things looked to be going to plan for Barca when Alexis Sanchez gave them the lead after just seven minutes.
The Chilean looked as if he was trying to pull the ball across the penalty area, but it looped off his right foot over the stranded Diego Alves and into the back of the goal.
At the other end, Sophane Feghouli saw a show parried by Victor Valdes, but Barca were in control for the first half hour and should have increased their lead.
Sergio Busquets fired over when well placed, while Dani Alves' run into the area ended with him just unable to control Pedro's cross.
Pedro then set up Alexis and the forward mistimed his header to allow Alves to show his reflexes and make the save, just before the Valencia keeper did magnificently to turn a Messi shot wide of the near post.
However, Barca began to get careless, the short passes began to go astray and Valencia began to threaten. First Ricardo Costa failed to take advantage of an error from Valdes and headed a corner wide of an empty net.
Feghouli launched a break which was only denied by last ditch defending from Gerard Pique, but Barca failed to heed the warning and Dani Parejo stabbed the ball home a minute from half time to finish up a break he began by robbing the ball from Cesc. He exchanged passes with Feghouli before sliding the ball into an empty net.
Piatti stunned the home side three minutes into the second half as he headed Valencia ahead with Valdes stranded and although Messi ended 125 days without a league goal when he scored a rather fortunate penalty, Valencia were not to be denied as he shot home from close range following a mixture of good work from Feghouli coupled with poor Barca defending.
There was still half an hour left to play, but Barca looked flat and short of ideas against a tight and competitive rival and although Messi was inches away from levelling in the last attack of the game nobody can deny Valencia were good value for their win.
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