Real Madrid and Barcelona will each head into the Clasico next weekend on the back of a defeat after La Liga's two title favourites were punished for slack performances on Saturday.
Zinedine Zidane made four substitutions at half-time but could not spark a lethargic Madrid into life as his team fell 1-0 at home to newly-promoted Cadiz.
Then two hours later on the opposite side of the city, Ronald Koeman tasted his first competitive loss as coach of Barcelona as they followed Madrid's example by being beaten 1-0 by Getafe at the Coliseum Alfonso Perez.
Madrid's was perhaps the more concerning display, the reigning champions managing just two shots on target against Cadiz, who could have scored more after Anthony Lozano's early strike.
But Barca were not much better, with Lionel Messi strangely quiet and the team failing to rebound after Jaime Mata's penalty gave Getafe the lead in the second half.
For Madrid, there was an injury concern too as Sergio Ramos spent the second half in the stands with ice strapped around his left knee.
Madrid said the injury was not serious but it puts in doubt Ramos' involvement in their first Champions League game against Shakhtar Donetsk on Wednesday, as well the Clasico three days later.
"Hopefully it's minor, said Zidane. "Tomorrow we'll see what he has done."
A prolonged absence for Ramos would cap a deflating night for the champions, whose dreary display certainly hands an early boost to their title rivals.
Even if Barcelona were unable to capitalise, Atletico Madrid had earlier beaten Celta Vigo 2-0, with Luis Suarez opening the scoring at Balaidos.
"There is no explanation," said Zidane. "If they scored two or three goals in the first half, we couldn't have complained. There are no excuses."
This is Cadiz's first season in the top flight in 14 years and their first victory over Real Madrid in 29. Their reward is second place in the table, denied top spot by their opponents only due to goal difference.
Isco, Luka Modric and Lucas Vazquez were the other three players to be hauled off by Zidane, who was reacting to a particularly poor display from his side in the first half.
Eder Militao, Casemiro, Fede Valverde and Marco Asensio came on while a surprised-looking Toni Kroos also departed in the second period, replaced by Luka Jovic.
But Cadiz could have been three up in the first quarter of an hour as Ramos prevented Alvaro Negredo's finish from rolling in before Negredo created the opener.
His cushioned header put through Lozano, who skipped beyond Madrid's sleepy defence and poked over the onrushing Thibaut Courtois.
Madrid might have equalised in the second half as Vinicius Junior headed wide of an open goal and Karim Benzema rattled the crossbar with a long-range shot. But Cadiz were not overly troubled.
Getafe were never really hanging on either, even if Barcelona went close to an equaliser, Messi hitting the post and then driving a loose ball wide in injury-time. Antoine Griezmann also ballooned over when put through in the first half.
Getafe's Cucho Hernandez also hit the bar after a clumsy challenge from Frenkie de Jong on Djene Dakonham gave Mata his chance.
Earlier, Suarez partnered Diego Costa for the first time and scored as Atletico Madrid beat struggling Celta Vigo.
But the Suarez-Costa combination came to an early end as Costa was forced off injured in the second half.
"I liked the mix of the two," said Diego Simeone. "Their characteristics mean they can play together. They give us strength and presence and personality in the penalty area. It's one of the options the team has."
Sitting in the stands, Costa was seen with his face in his hands and he seems likely now to miss Atletico's Champions League opener at Bayern Munich on Wednesday.
Suarez had earlier finished off a sweeping move down the left before Yannick Carrasco made sure of the victory in injury-time, heading in after Joao Felix's effort came back off the crossbar.
There was also a debut for Lucas Torreira, the Uruguayan signed on loan from Arsenal, who was energetic and tidy in central midfield, despite feeling some cramp late on.
Atletico climb to fourth, two points behind Real Madrid and one ahead of Barcelona. Celta, meanwhile, have managed only one win from their first six games and sit 13th.
Madrid, Spain | AFP
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