Transport's Zinhle Mngomezulu says a truck and a car collided about 2 kilometres outside Ladysmith near the Driefontein turn-off.
A seventh person thought to have been a passenger in the truck was taken to hospital.
Mngomezulu says traffic on the N11 heading towards Newcastle has been severely affected while crews clear the scene.
''It has been confirmed that 6 people have died in that accident. Traffic has come to a standstill at the moment as we are still busy with extrication,'' she said.
(Photo: KZN EMS)