Ambulance New Brunswick said the Atlantic Charters flight crashed in a wooded area near the airport shortly after 5 a.m.
A second pilot and a registered nurse survived the crash. There is no word on their injuries.
Ambulance New Brunswick says the plane had dropped off a patient at Saint John Regional Hospital and was returning to Grand Manan when it crashed.
There were no patients on board the plane at the time.
“We are devastated by this incident,” Paul Ward, interim president of Ambulance New Brunswick, said in a statement.
The paramedic who died worked for Ambulance New Brunswick and the pilot worked for Atlantic Charters, which has the contract to provide air service to Grand Manan.
Ward said it's too early to say what happened.
Grand Manan is off Saint John in the Bay of Fundy.