Newly promoted Alaves stunned Spanish champions Barcelona by winning 2-1 at the Camp Nou on Saturday as boss Luis Enrique paid a heavy price for starting Lionel Messi and Luis Suarez on the bench.
Barca now trail Real Madrid by three points at the top of the table after Cristiano Ronaldo took just five minutes to score on his return from a two-month injury layoff in a 5-2 rout of Osasuna at the Bernabeu.
Enrique made seven changes from their last outing -- a 1-0 win at Athletic Bilbao two weeks ago -- with Messi recovering from a groin problem and Suarez rested following his exertions in World Cup qualifying with Uruguay.
That decision backfired as Barca failed to unlock Alaves's mass ranks of defence before the break and went behind when Deyverson turned Kiko Femenia's cross past Jasper Cillessen on his Barca debut.
Neymar was the only one of Barca's star "MSN" front three to start on his first appearance of the season after leading Brazil to Olympic gold and should have levelled moments later when he failed to hit the target with a free header inside the area.
The Brazilian provided the assist as Jeremy Mathieu headed home Barca's equaliser from a corner a minute after the break and the French defender somehow blasted wide with the goal gaping moments later.
Messi was summoned on the hour mark, but there was another shock to come for the hosts when Ibai Gomez took advantage of some awful Barca defending to put Alaves back in front.
Andres Iniesta and Suarez were also called upon as the "MSN" were reunited for the first time in four months, but even they couldn't break the Alaves resistence as the Basques held out for their first La Liga win in a decade.
- Ronaldo back with a bang -
Ronaldo was making his first appearance since limping off in tears during the Euro 2016 final, but was handed the perfect return on a plate by Gareth Bale as the Welshman squared for him to tap into an unguarded net.
"The truth is I started a bit warily, which is normal after a serious injury, but I feel good, without pain and getting back to full fitness," said Ronaldo.
Despite failing to hit top gear Real comfortably matched a club record of 15 straight La Liga wins as Danilo's low drive and a towering header from Sergio Ramos extended the lead before half-time at the Bernabeu.
Osasuna goalkeeper Nauzet Perez meekly turned Pepe's header into his own net for Real's fourth before Luka Modric's fiercely struck shot from outside the box made it 5-0.
However, Real's defensive deficiencies were exposed in the second half as Oriol Riera and David Garcia cut Osasuna's deficit, whilst Roberto Torres saw a penalty saved by Kiko Casilla.
- Griezmann awakens -
Antoine Griezmann handed Atletico Madrid a much-needed first win of the season in a 4-0 victory at Celta Vigo.
Koke met Griezmann's fine cross eight minutes into the second half in Vigo to give the visitors the lead before Euro 2016's top scorer Griezmann headed home his first two goals of the season in the final 20 minutes.
Angel Correa added a fourth two minutes from time.
"We needed a game like this," Griezmann told BeIN Sports Spain.
"I am still getting back into my rhythm (after the Euros) and still have a way to go, but I am giving my all and I'm very happy to get the goals and the assist."
Las Palmas's 100 percent start to the campaign was ended in cruel fashion in a 2-1 defeat at Sevilla. Tana's fine first-half strike for the Canary Islanders was cancelled out by a dubious Pablo Sarabia penalty a minute from time before Carlos Fernandez bundled home a stoppage-time winner.
Villarreal secured their first victory of the season, winning 2-0 at Malaga thanks to first-half goals from Jaume Costa and Nicola Sansone.
(For more sports news and updates, follow Ahram Online Sports on Twitter at @AO_Sports and on Facebook at AhramOnlineSports.)