Water on the road caused a crash that eliminated former race leader Nicolas Roche and overall contender Rigoberto Urán, says Urán's team-mate Lawson Craddock.
EF Education First also lost Brit Hugh Carthy due to the massive crash with 92 kilometres left to race to Ares del Maestrat.
The team's day worsened when Tejay van Garderen crashed with around 25km to race while fighting for the stage six win from the escape group. He finished last in the stage, uncertain about continuing on stage seven.
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"We came ripping on this downhill, and we hit a turn that was tighter than expected, with a bit of water on the road, and guys just slid out," said Education First rider Craddock at the finish.
"It was a rough moment for that to happen because guys were going pretty fast."
EF riders Owen and Sergio Higuita also fell in the crash. Irishman Roche, who led the race for three days, tried to continue but after 10 to 20 kilometres, pulled the plug on his Spanish tour.
Urán, according early reports, broke his collarbone in the incident. He was touted as a favourite, having placed seventh in the Tour de France in July and seventh in the 2018 Vuelta.
Brit James Knox (Deceuninck - Quick-Step), Italian champion Davide Formolo (Bora-Hansgrohe), Victor de la Parte (CCC Team) and Jumbo-Visma's Tony Martin, George Bennett, and Neilson Powless fell as well. De la Parte abandoned.
"We just keep hitting the deck in this Vuelta," said Bennett, referring to the stage one crash that forced Steven Kruijswijk to abandon. "Hopefully, in a few days we'll all forget about this."
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"It was pretty unfortunate. We lost Rigo and Hugh for sure, which is a bummer," Craddock said. "We will regroup tonight. It's a long race. I think there is still a lot of fight within those of us who are still racing.
"Once we got word that Rigo was out, you can be disappointed, but we tried to flip it around very quickly. That's a testament to the leadership of Juanma [Gárate], our sports director, and Mitch Docker our road captain. It was frustrating to say the least."
The bad luck had continued from stage four, when Docker crossed wheels with Urán and they fell. The Colombian fell twice that day.
Carthy placed 11th overall in the Giro d'Italia this spring when it ended in Verona. A few weeks later, the 25-year-old Brit won a stage in the Tour de Suisse. He and Van Garderen could have offered the team a chance to win stages.
"It was a rough day for us," Craddock said. "[Murphy's Law] showed up with a vengeance."
