Thieves drove a Jeep into a sandwich shop in Peacehaven and made off with the safe early this morning (Tuesday 2 April).
The ram-raiders smashed their way into the Subway shop on the A259 South Coast Road shortly before 1am.
Sussex Police said that a Cherokee Jeep, thought to have been used in the raid, was found abandoned near by.
The safe was not in the Jeep which is being examined by forensic experts.
Inspector Dave Frey, from the East Sussex Neighbourhood Response Team, said: “I would appeal to anyone who saw or heard any suspicious activity to please come forward as soon as possible.
“Officers will be continuing with local inquiries and viewing CCTV.”
Anyone with information about the raid is asked to call Sussex Police on 101 or the independent charity Crimestoppers anonymously on 0800 555111.