The 24-year-old was struck by his motorbike which bounced against the outer wall at the Montmelo track after he fell at Turn 12 in the second practice session.
The SAG team rider lay on the ground, where he was treated before being transferred by helicopter to the Hospital General de Catalunya. He passed away at 1655 local time (1455 GMT).
“It is with great sadness that we have to report the passing of Luis Salom,” organisers said in a statement.
Salom’s death cuts short a career which had started early. His grandfather had been a competitor and owned a motorcycle shop. The rider from Palma de Mallorca first climbed onto a motorbike at the age of two.
But during his career he was always on the verge of a world title, without lifting the ultimate prize.
Salom made his world championship debut at Jerez in 2009 in the 125cc category, and finished on the podium 25 times — with nine wins in the Moto3 category.
He was runner-up in the 2012 Moto3 world championship and third overall in 2013.
He also finished on the podium three times in 41 appearances in the Moto2 world championship, including a second place in the opening round this year at Losail in Qatar.
“The truth is that last year was not too good. Yes we got podiums but it was not what I expected,” said Salom of his second season in Moto2 in 2015.
Tributes poured in following the announcement of the Mallorcan rider’s death.
“Devastated, very sad and speechless … All my encouragement to his family. RIP Luis Salom,” wrote Spain’s MotoGP world champion Jorge Lorenzo on Twitter.
“Devastated by the loss of a great friend ! My sincere condolences to the family. Will always remember you,” Honda’s Spanish MotoGP rider Dani Pedrosa wrote on Twitter.
“You were one of my toughest opponents, one of my best teammates and then a friend. You will always be in my heart,” said Spain’s Maverick Viñales, who beat Salom to the Moto3 title in 2013.
Spanish Formula 1 driver Fernando Alonso wrote: “Such terrible news. Such anger and sadness. Rest in peace, rider. A huge embrace to Luis Salom’s friends and family.”
The last death in the sport was Italian Marco Simoncelli following an horrific crash at the Malaysian MotoGP in Sepang in 2011.
Simoncelli fell and was hit by Colin Edwards and Valentino Rossi as he slid across the track on his Honda.
Despite Salom’s death organisers have decided to go ahead with this weekend’s Grand Prix, although the bikes will use the route used by Formula One drivers, nullifying the fatal Turn 12.