A Port Pirie woman, 38, who was the sole occupant and driver of the Honda, was taken to the local hospital with serious injuries, while the Mitsubishi driver, a Kadina woman, 27, was flown to the Royal Adelaide Hospital with serious injuries.
The three children travelling in the Mitsubishi, a boy, 4, a girl, 3 and a baby boy, 1, were all flown to the Royal Adelaide Hospital for treatment.
Major crash detectives spent several hours scouring the scene on the Spencer Highway overnight to examine the circumstances that led to the smash.
Any witnesses or anyone with dashcam footage should call Crime Stoppers on 1800 333 000.
For Australians looking for intelligent and unbiased news coverage, join renowned journalist Natarsha Belling on Your Morning Agenda for breaking national and international stories as well as the top business and finance stories - every weekday from 6:30am on Listnr