Barcelona's stuttering title bid suffered another setback when they lost 2-1 at home to Valencia on Sunday, while Atletico Madrid moved level on points with the La Liga leaders after a comfortable win over Granda.
Shell-shocked Barca have 76 points along with Atletico, who knocked the holders out of the Champions League in midweek, and remain top only due to a superior head-to-head record.
Atletico earlier eased to a 3-0 home win over Granada after Fernando Torres grabbed his fourth goal in as many games with Koke and substitute Angel Correa also got on the scoresheet.
Real Madrid, whose coach Zinedine Zidane said in February that the title race was over, thrashed Getafe 5-1 away on Saturday and stand just one point behind the leading pair,
An own goal by Barca midfielder Ivan Rakitic put Valencia ahead after 27 minutes at the Nou Camp and Santi Mina added a second just before halftime to stun the Barca supporters.
Lionel Messi scored his 500th career goal to reduce the deficit after 64 minutes but the struggling hosts, who have squandered a nine-point lead, could not find an equaliser.
Despite Barcelona registering a third successive league defeat for the first time since 2003, Luis Enrique remained upbeat about his team’s chances of winning the title.
“We’ve got a marvelous challenge, if we win the five games remaining we will be champions,” he told a news conference.
“Of course, our credit has run out and we are aware of the challenge. We’re going to approach it like a Barca player always does, with our heads held high.”
Barca humiliated a Valencia side coached by Gary Neville 7-0 in a King’s Cup semi-final game in February but had a much tougher time against successor Pako Ayesteran’s side and went behind when Guilherme Siqueira’s cross bounced off Rakitic and beyond Claudio Bravo.
Barcelona forwards Messi, Luis Suarez and Neymar each had efforts saved by the impressive Diego Alves, but Valencia continued to cause the home side problems on the break.
Santi Mina increased the visiting side’s advantage just before halftime, receiving a pass from Dani Parejo and beating Bravo at the far post with a powerful driven effort.
Messi turned in a low cross from Jordi Alba to end a drought of five games without scoring and net his 500th career goal, but a second proved elusive for the hosts.
Valencia's Alves produced a spectacular save to deny Rakitic late on and Barca defender Gerard Pique agonisingly missed the target at the near post in stoppage time.
"We were better than Valencia in every aspect apart from effectiveness. We’ve dropped three points that we could have taken fairly but football is like that,” added Luis Enrique.
Atletico, boosted by a 2-0 Champions League second-leg win over Barca on Wednesday which put them into the semi-finals, got off to an ideal start against struggling Granada when Koke drilled a loose ball into the net on 15 minutes.
Granada winger Ruben Rochina hit the post later in the half before Torres eased Atletico's nerves by notching the second, latching onto a threaded pass by Koke to lift the ball over goalkeeper Andres Fernandez and into the far corner.
Argentine forward Correa came on to replace Atletico's top scorer Antoine Griezmann and made the most of his cameo appearance by racing onto a pass from Saul Niguez down the left and tucking the ball into the far bottom corner.
Atletico will be without suspended captain Gabi for their trip to Athletic Bilbao on Wednesday, while Pique is banned for Barca’s visit to Deportivo La Coruna.
“We have the chance to put in a big performance in Bilbao next week and keep competing in the four games we have left,’ Atletico coach Diego Simeone said.
“It will be hard, but we will do what the fixture list demands and asks of us: win, win and win.”
Elsewhere on Sunday, Sevilla drew 1-1 at home to Deportivo La Coruna, Athletic Bilbao won 1-0 at Malaga to move up to fifth, and Rayo Vallecano moved five points clear of the relegation zone after beating fourth-placed Villarreal 2-1.