The 28-year-old Portuguese forward was driving through Zamora, Spain in a Lamborghini when his flat tyre suddenly burst and sent the car veering off the road, police believe.
The crash occurred on the A52, near the municipality of Palacios de Sanabria at around 12:40am.
The dad-of-three was believed to have been driving a luxury SUV Lamborghini Urus and travelling towards a port in the northern city of Santander.
He was due to catch a ferry this morning after being advised not to take a plane due to a recent lung surgery, according to CNN Portugal.
The Portuguese ace had missed several matches last season after suffering a rib injury in October during a match against Chelsea.
Jota was due to return to Liverpool to take part in the club's pre season games which start later this month.