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Lampaert won from teammate Matteo Trentin in a time of 4hr 36min 13sec as Quick-Step Floors caught the peloton napping with two kilometres to go with Britain’s Adam Blythe in third.
Splits in the peloton meant the overall contenders were distanced as Vincenzo Nibali clawed back some of the 22 seconds he lost to Tour de France champion Chris Froome on the opening stage team time trial.
The 10-second time bonus on offer to stage winners moved Lampaert to the top of the general classification standings, a second ahead of Trentin with Italian Daniel Oss third.
With nine summit finishes to come, the flat route in southern France was supposed to offer a rare chance for sprinters to shine, but strong crosswinds made the peloton susceptible to attacks.
Quick-Step took advantage with a three-pronged attack three kilometres from the line, opening up the gap Lampaert needed for his first Grand Tour stage win.
“I knew I could ride one kilometre very fast and it worked out,” said Lampaert after taking the leader’s red jersey.
Nibali finished in the lead group with Froome eight seconds back alongside 2015 Vuelta winner Fabio Aru and Adam Yates.
However, Alberto Contador lost a further five seconds on Froome in his final race before retirement to fall 31 seconds back on the four-time Tour de France winner.
Froome is aiming to become just the third rider to ever win the Tour and Vuelta in the same year.
The Briton is ninth in the overall standings, 21 seconds behind Lampaert.
“I think we were probably a little bit short coming into the final few kilometre, but I’m still happy with that result as I think we did a great ride,” said Froome.
“There were a few seconds lost to Nibali and Esteban Chaves, but some gained also on Contador and some of the other GC guys so I think we can be happy with that with the mountains tomorrow.”
Stage three sees the first category-one climbs as the race exits France on a 158.5km ride from Prades-Andorra la Vella on Monday.
The first stage in Spain isn’t till Tuesday with heightened security measures to be put in place following a pair of terror attacks in Barcelona and the nearby seaside resort of Cambrils that left 14 dead and over a hundred injured.
The finish line for the fourth stage of the Vuelta is just 20 kilometres along the Mediterranean coast from Cambrils in Tarragona.
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