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Two women were killed in another accident reported in the Eastern Cape.
The provincial Transport Department said the accident happened between Graaff-Reinet and Aberdeen on Saturday.
Spokesperson, Unathi Binqose, said an SUV with five people inside collided with an Iveco mini-bus with an unknown number of occupants.
He said three people from the SUV were taken to hospital, while there were no injuries in the other mini-bus.
However, Binqose said in a secondary accident, a Toyota Quantum mini-bus crashed into the Iveco, killing two two adult females.
Four passengers from the third vehicle were transported to a hospital in Graaff-Reinet.
Earlier this week, Eastern Cape premier, Oscar Mabuyane called for calm on the province's roads over the Christmas long weekend.
"We want to appeal to all the motorists to make sure that they obey the rule of the road," Mabuyane said, also appealing to pedestrians to do the same.
"We don't want to see the carnage we normally see during the festive season. There's a lot of traffic into the province, as you know many people are coming back home for holidays," he added.
The Premier's appeal comes a day after five people died in a fiery crash on the road between Kariega and Graaff-Reinet.
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At a briefing on Friday, Transport Minister Sindisiwe Chikunga noted that 719 people were killed on the country's roads in the first three weeks of December.
Addressing a media briefing on Friday, she said this was a 4.3% decline on the same period last year.
"Gauteng has recorded 187 fatalities which is a 23.8% increase compared to last year. KZN has recorded 135 fatalities which is a 6.3% decrease compared to last year. Limpopo has recorded 88 fatalities which is the same as the previous year.
"Mpumalanga has recorded 81 fatalities which is a 6.6% increase compared to last year. Western Cape has recorded 76 fatalities which is a 1.3% decrease compared to last year. Eastern Cape has recorded 59 fatalities which is a 41% decrease compared to last year.
"Free State has recorded 49 fatalities which is a 7.0% decrease compared to last year. North West has recorded 37 fatalities which is a 17.8% decrease compared to last year. Northern Cape has recorded 16 fatalities which is a 49.7% decrease compared to last year
Chikunga said the Eastern Cape is one of six provinces that will receive "focused attention this year with night-time deployment of traffic officers and road safety activations that are intended to improve pedestrian safety".
