The Subway shop in Peacehaven was ram raided in the early hours of this morning (Tuesday April 2).
Thieves drove a 4x4 car into the sandwich shop on South Coast Road and made off with the safe.
Sussex Police arrived at the scene at 12.50am.
A Cherokee Jeep, thought to have been used in the ram raid, was recovered nearby and is currently being examined forensically.
Inspector Dave Frey from 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 enquiries and viewing CCTV.
“If you have any information about this incident then please call 101 quoting serial 33 of 2/4 or alternatively leave an anonymous message with the independent charity Crimestoppers on 0800 555 111.”