Reports in the Spanish media state that emergency services were called to a hotel room in Seville, but efforts to revive her were unsuccessful.
She was 33.
‘Dear friends: Maria has left us’, her family posted on Facebook. ‘She had to go to heaven like all the angels. We thank God for the extra year and a half he left her with us.’
De Villota suffered life-threatening injuries during a straight line test with Marussia at Duxford Aerodrome in July 2012 when her car struck a team truck.
She lost her right eye in the accident and suffered skull damage, but was able to make a recovery.
She continued her involvement in motorsport, becoming an ambassador for women in motorsport and participating in the FIA Drivers’ Commission and its Action for Road Safety campaign. She also returned to the Formula 1 paddock at the Spanish Grand Prix earlier this year.
De Villota, daughter of former Formula 1 driver Emilio de Villota, had previously raced in categories such as Spanish Formula Three and Superleague Formula and also tested for Renault at Paul Ricard in 2011.