Eight people died in a head-on collision between a double-cab bakkie and another vehicle on the R61 outside Ngcobo on Tuesday evening, the Eastern Cape health department said.
Six died on the scene and two on arrival at All Saints Hospital, spokesperson Sizwe Kupelo said.
Four were in a critical condition following the accident, which happened shortly before 19:00. It was not yet clear which car the eight were in.
Kupelo said the reckless behaviour of motorists on the province's roads was costing the department millions of rands.
Two people were killed in Ngcobo on Monday night.
He urged drivers to be cautious.