The incident happened at around 4.30am, police added.
Police are now appealing for witnesses.
A Sussex Police spokesperson said: “Emergency services responded to a report of a single vehicle collision on the B2092 Crowhurst Road, St Leonards, at about 4.30am on Wednesday, September 11.
“A car had left the carriageway.
“Two passengers, a 28-year-old woman and a 32-year-old man were taken to hospital with serious injuries, where they remain.
“The driver, a 38-year-old man, was also injured and was taken to hospital, where he remains. Anyone with information about the collision is asked to report it to Sussex Police online or email [email protected] and quote Operation Elland.”
The section of road where the collision happened remains closed, with emergency services still at the scene.

1. Eastbourne road closed following collision
Atlantic Drive closure. Photo: Sussex News and Pictures

2. Eastbourne road closed following collision
Photo from the scene Photo: Sussex News and Pictures

3. Eastbourne road closed following collision
Photo from the scene Photo: Sussex News and Pictures

4. Eastbourne road closed following collision
Photo from the scene Photo: Sussex News and Pictures