Emergency services were called to State Highway 8 just before 5pm, after a station wagon and a minivan collided.
A 36-year-old man from one vehicle and a 35-year-old man and three women - aged 27, 30, and 31 - from the second vehicle, were hospitalised with serious injuries as a result.
Police today said details of the cause of the crash would be advised once the investigation was completed.
Earlier story
Several off-duty doctors and nurses were the first to arrive at the scene.
General medic Ravi Mehta, from London, told the Otago Daily Times that when he arrived at the scene three doctors were assisting the injured.
Mr Mehta said from what he had seen he did not believe any of the injuries were life-threatening.
A St John spokesman said three helicopters and two ambulances attended the crash.
Sergeant Derek Ealson, of Alexandra, said last night police were still trying to establish details of the crash.
Four people were in one car, while two others, believed to be male, were in the other, he said.‘‘We have just got those very basic details until we can speak to them,'' Sgt Ealson said.
Fire crews from Cromwell, Tarras and Luggate attended the scene.
About 50 vehicles waited for three hours in steady rain following the crash, as police and fire crew cleared wreckage from the road.
Sgt Ealson said the serious crash unit would conduct a scene examination today.