A 13-year-old girl and a 31-year-old man suffered serious injuries after a major head-on collision.
The teenage passenger, from Worthing, was airlifted to Southampton General Hospital with serious injuries after the crash in Angmering yesterday.
A driver from Rustington also suffered serious injuries and was taken to Royal Sussex County Hospital by ambulance.
Firefighters used hydraulic equipment to cut the casualties from the wreckage of two cars after the collision at around 3pm yesterday.
A Renault Megane and a Toyota Auris collided while travelling opposite direction on the A280.
The man, 31, was driving the Megane, while the girl was a passenger in the Auris.
The driver of the Auris, a 48-year-old man from Worthing, suffered cuts and bruises but was not kept at hospital.
The road was closed between the A259 roundabout and Water Lane for several hours.
Police are appealing for witnesses to the collision.
Anyone who saw what happened or saw either vehicle before the collision is asked to contact police on 101 or email email@example.com quoting Operation Plumpton.