It happened around 2 a.m. on the sixth floor of the hospital near N. Roxboro Street and N. Duke Street.
Authorities told ABC11 what was originally reported as an explosion, turned out to be a fire after sparks were spotted. It was kept under control by the hospital's sprinkler system until firefighters arrived.
The one person who died during the fire was a patient at the Select Specialty Hospital that rents space inside Durham Regional Hospital. The 30-bed unit is a long-term care facility.
"Select Specialty Hospitals is a separately operated facility on the sixth floor," said Katie Galbraith with Durham Regional Hospital. "That's where it happened, and the fire was contained to one room."
Officials also said three hospital staffers suffered smoke inhalation, while three patients, who were on ventilators prior to the fire, were taken to the intensive care unit after being checked into the emergency room. Other patients at the Select Specialty Hospital were not injured and moved elsewhere in the hospital.
"They were minor, smoke inhalation only," said Robert Jernigam with Select Specialty Hospitals. "No danger whatsoever."
Officials are currently investigating what could have caused the fire.