An alarm was raised and fire fighters were called when the neighbours heard a bang in the building in Riddings, near Alfreton.
Emergency services were initially unable to get into the house because of the risk of fire and a further blast, but when a rescue team entered the house, which was partially collapsed, a man and his wife were found dead, police said.
The couple's family have been informed but they have not been formally identified.
Police said they did not believe there were any suspicious circumstances surrounding the fire but investigations are on.
Earlier, officials said a leak of gas had not been ruled out as a possible cause.
