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Six people were killed in a three-car pile-up on the R-61 between Komani and Cofimvaba.
The Eastern Cape Transport Department says one person sustained serious injuries in Friday's crash involving three Toyota vehicles.
Spokesperson, Unathi Binqose, said four people died on the scene, while two other people were declared dead on arrival at Cofimvaba hospital.
He said the main cause of the crash is still unknown at this stage.
Police have opened a culpable homicide docket.