Officers were called to A23 London Road in Crawley, at the junction with Manor Royal at, around 3.15am, to reports of a single-vehicle collision involving a grey Toyota Proace van.
A 25-year-old man, from East Grinstead, suffered serious injuries and was pronounced dead at the scene of the crash, police confirmed.
A spokesperson added: "Officers are appealing to anyone who witnessed what happened, or who has relevant dash-cam footage that may assist with enquiries, to come forwards.
"London Road remains partially closed in both directions while vehicle recovery work is ongoing.
"Anyone with information, or who saw the vehicle prior to the collision, is urged to report online or call 101, quoting Operation Lynton."