Firefighters said there was nothing they could do to save the Stone Soup Cafe.
Officials say the call came in just before 2 a.m. when a person driving on Route 1 saw smoke drifting across the road.
When firefighters arrived at the business, located at the Machias and East Machias town line, it was fully engulfed in flames.
Officials said the owners had renovated the building and recently opened the cafe after the building sat empty for a number of years.
Nobody was there when the fire broke out.
Crews from several towns helped battle that blaze.
Officials said that there are a motel and several houses next door but they were able to keep the fire from spreading.
The cause of the fire is under investigation.
One of the owners said the staff is like their family and their hearts are breaking for all of them.
Steven Torres said that a Go Fund Me page will be set up to help employees.