Police say a child is among the five people killed in the collision between two minibus taxis on the N6 between Bloemfontein and Reddersburg in the Free State.
They say both drivers in the two vehicles are among the deceased.
Four of the deceased were in one minibus taxi, the other vehicle had only the driver.
Provincial Emergency Medical Services spokesperson Sipho Towa says at least six people have been critically injured while five others sustained moderate to minor injuries.
Towa says the injured have been taken to various hospitals in Bloemfontein.
The road has since been reopened, while work to clear the scene of the crash is underway.