Police dogs and a police drone were used to try and find two people who they say ran from the scene.
The crash happened just before 5.30pm on Wednesday night along the A22 near Lower Dicker just outside of Hailsham.
One person was treated by ambulance crews while the occupants of the other vehicle ran from the scene.
The crash involved a Volkswagen and Ford Galaxy.
The VW had damage to its front, while the Ford had damage to rear left side.
A Sussex Police spokesman said: “A widespread search was carried out involving the police drone, but they have not been located at this time.
“Anyone who witnessed the incident or has relevant dashcam footage is asked to contact police online or via 101, quoting serial 976 of 03/01.”
The road was closed for several hours but was reopened by yesterday morning.
East Sussex Fire and Rescue Service also attended the crash.
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