Raiders smashed their way into X-Factor presenter Dermot O’Leary’s restaurant and stole the safe.
The TV presenter’s restaurant, Fishy Fishy, was broken in to early on Sunday morning.
The safe contained around £1,500 pounds from Saturday night’s takings.
Sussex Police said they are investigating the break in, which took place just before 1am yesterday. They believe a professional gang may be responsible and are looking at connections with a raid on the safe at the Heist bar in West Street in June 2011.
PC Rachel Piggott of Brighton and Hove Neighbourhood Policing Team said: "We believe that a group of around four people were involved in the break-in and we are looking through CCTV from the area to identify them.
"At the time of the burglary Brighton would have been busy with people enjoying a Saturday night out and I would appeal for anyone who was in the area of East Street and noticed anyone acting suspiciously.
"The safe would have been heavy and they would probably have needed a vehicle to remove it from the area."
Anyone with information is asked to contact Sussex Police on 101 quoting serial 455 of 7/10 or the independent charity Crimestoppers anonymously on 0800 555 111.