The 44-year-old male driver of a van was taken by ambulance to hospital with moderate injuries following the 10.30am crash, in which a large truck and trailer unit heading north T-boned the smaller vehicle on the highway near Double Hill Rd.
The van driver had only just picked up two hitch-hiking Dunedin students, a male and female.
Senior Sergeant Tania Baron said police were investigating whether the van driver started a U-turn across the highway, having failed to notice the truck behind his vehicle.
The female student in the front passenger seat was also taken to hospital with moderate injuries, while the male student seated at the van's rear was uninjured.
The male truck driver also escaped injury.
"We are very fortunate we are not looking at a double or triple fatality," Snr Sgt Baron said.
The truck driver had just navigated a corner and was travelling at a slow speed accordingly.
"That was probably, by all accounts, the saving grace," the police officer said.
On collision, the van was pushed about five metres by the truck.
SH1 was closed to a single lane for about an hour while emergency services attended the scene.
Snr Sgt Baron said police had spoken to witnesses and were continuing their investigations of the incident.