The collision happened near Delgatie Castle in Turriff, Aberdeenshire, at about 11:45 on Sunday.
Police said a 42-year-old woman who was a passenger in a red Volkswagen Golf, which was involved in the crash, was airlifted to Aberdeen Royal Infirmary.
A 30-year-old man who driving a black Citroen C2 was taken to the hospital by ambulance.
Police said they both remain in a critical condition.
An 18-year-old woman, who was also a passenger in the Volkswagen, sustained a serious leg injury and is said to be in a stable condition at Aberdeen Royal Infirmary.
Three other people who were travelling in the Volkswagen received treatment for minor injuries, police said.
The unclassified road was closed for around seven hours while officers investigated the scene.
Sgt Colin Matheson said: "I would like to appeal to anyone who may have seen the incident and has not yet spoken to police to please come forward with any information.
"Likewise anyone who may have seen either vehicle in the time leading up to the collision should also get in touch with police on 101 as we try to piece together exactly what happened."
Two people are in a critical condition in hospital after a car crash on New Year's Day.