Three people were killed in a head-on collision between a bakkie and a car on the N6 between Komani, formerly Queenstown and Jamestown.
Eastern Cape provincial traffic spokesperson, Charles Bramwell, said the accident happened shortly before 7 am on Tuesday.
He said it was alleged that a white Mitsubishi bakkie was travelling towards Aliwal North and had crossed the barrier line, colliding with an oncoming VW Polo.
Bramwell said three people in the Polo died while three others were injured. Two people in the bakkie were also injured and taken to hospital.
He said, "fatigue is suspected to be the cause of the accident".
Jamestown SAPS have opened a culpable homicide docket.
On Monday, Transport Minister, Fikile Mbalula, announced a 25% reduction in road crashes at the half-way mark of the road safety campaign, saying that as of last Friday 81 people had died on Eastern Cape roads down from 102 at the same time last year.