The crash happened at around 4.45pm on Saturday on the A428 at the crossroads with Church Lane, East Haddon and involved a white Audi A3 and a grey Volvo.
The male driver and female front seat passenger in the Volvo were taken to University Hospital Coventry with serious injuries.
Two rear seat passengers in the Volvo, a 13-year-old boy and a 16-year-old boy, were taken to Birmingham Children’s Hospital and Queens Medical Centre respectively with potentially life threatening injuries.
The male driver of Audi was taken to Northampton General Hospital with minor injuries.
The air ambulance also attended the scene.
Anyone with information or who witnessed this incident is asked to call the ‘Drivewatch Hotline’ on 0800 174615.