The incident involved two vehicles and two pedestrians on the junction of Lynwick Street and Guildford Road in Bucks Green, near Horsham.
Police were called to the scene shortly after 8.30am this morning and the road was closed for more than six hours while they investigated.
It is reported a van collided with two men and another vehicle.
A 57-year-old man, one of the pedestrians, was taken to hospital with life-threatening injuries.
Another pedestrian suffered minor injuries. No other injuries were reported.
Now, officers are appealing for witnesses or anyone with information to come forward.
This includes anyone with CCTV in the area, and anyone with dashcam footage from vehicles in the area at the time.
A Sussex Police spokesman said: “Information can be reported to us online or emailed to collision.appeal@sussex.police.uk quoting Operation Aero.”
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