Police are appealing for witnesses to the collision, which happened southbound on the A23 in Warninglid, just after 1.30am this morning (December 16).
A Sussex Police spokesman said: “A black Nissan Micra which had four people travelling in left the main carriageway into the lay-by and collided with the rear of a heavy goods vehicle which was parked in the lay-by.
“The front seat passenger, a 25-year-old local man, sadly died at the scene.
“The rear nearside passenger, a 22-year-old woman from Surrey, sustained serious injuries and is in a critical condition at the Royal Sussex Hospital in Brighton.
“The driver, a 29-year-old woman from Surrey, remains in hospital and is in a stable condition.
“Anyone who saw the events leading up to the collision or the collision itself are asked to contact Sussex Police on 101 quoting Operation Cranbourne.”
A South East Ambulance Service (SECAmb) spokesman confirmed multiple ambulance crews attended the scene, along with an air ambulance vehicle.
He said: “One man was sadly pronounced dead at the scene. One patient was treated before being taken in a serious condition to the Royal Sussex County Hospital in Brighton.
“Two more patients, believed to have sustained less serious injuries, were also taken to the Royal Sussex County Hospital.”
A West Sussex Fire and Rescue Service spokesman confirmed three fire engines were called to the collision, along with a heavy rescue unit.
Sussex Police confirmed the incident was ‘ongoing’.