Robert Mckenzie, spokesman for KZN’s provincial EMS, said a woman and a teenager were killed in the collision at Weza, near Harding.
He said that the two had died by the time paramedics arrived on scene. A further three people were injured in the accident, two of whom were described as being in a critical condition.
KZN Road Traffic Inspectorate spokeswoman Zinhle Mngomezulu said the collision had occurred between a VW Polo and a Toyota Venture. She said the two people who were killed were in the VW.
The injured were taken to St Andrews Hospital in Harding.
Mngomezulu said the N2 had been closed off to motorists while traffic authorities cleared up the accident scene.
Investigations into the cause of the collision continue.