Emergency services were initially unable to get into the building in Riddings, near Alfreton, because of the risk of fire and a further blast.
The couple have been named locally as Simon and Shelley Saxton-Cooper.
Chief Inspector Steve Pont of Derbyshire police described the deaths as "an awful tragedy".
Homes evacuated
He said: "Our thoughts are with the family and friends of the two people who have lost their lives."
The couple's family have been informed, but they have not been formally identified.
The alarm was raised shortly after 07:30 BST when neighbours heard what they described as a "bang".
The emergency services declared a "major incident" and East Midlands Ambulance Service sent its Hazardous Area Response Team (HART) to the house.
David Lovett, from Derbyshire Fire and Rescue, said crews found the building "well alight" and "partially collapsed" when they arrived.
Neighbours were evacuated from their homes as a precaution.
Police said they did not believe there were any suspicious circumstances, but investigations were at an early stage.
Earlier, a force spokeswoman said a leak of gas had not been ruled out as a possible cause.
The HART team is called to deal with chemical, biological, or other hazardous materials at major incidents.
Source:BBC
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