The Trustpower TECT Rescue Helicopter flew a 58-year-old Rotorua woman to Waikato Hospital with pelvic, chest and abdominal injuries and her husband was flown by the Taupo-based Greenlea Rescue Helicopter to Waikato Hospital.
The remaining victims were taken to Rotorua Hospital by St John Ambulance.
Senior Sergeant Mike Membery of the Bay of Plenty Police District Command Centre told the Rotorua Daily Post there were multiple patients.
"There are at least six patients. This is a hard one to explain as they were all wearing their seatbelts and the weather was good."
He said the investigation into the cause was ongoing and he couldn't say what it could have been, but he wanted to give the public a general warning on driving to the conditions.
"We are coming into warmer weather and will be travelling a lot more. It's important to check your car is in good condition, but it's also important to make sure you are in good condition too."
He said if people felt tired or fatigued they should stop for a rest.
A witness to the crash told the Rotorua Daily Post she was following a car that was wavering across the road.
She said she started honking the horn to warn the driver. A crash happened soon after. She said it was a real shock and it happened really quickly.
"When I saw the car wavering across the centre line I honked my horn to try and warn the driver.
"It all happened very fast.
"You try and jump out and see what you can do to help. We just called the ambulance."
Anyone who may have witnessed the crash or been driving in the area at the time is asked to contact Rotorua Police on (07) 349 9400.
Alternatively, you can contact Crimestoppers anonymously on (0800) 555 111.