It happened at a house on 9th street, near "E", in the city of Orange Cove early Sunday morning.
Video from an Action News viewer shows just how bad the flames were as firefighters tried to get the fire under control.
Firefighters say they arrived just five minutes after receiving a call on Saturday, but by the time they got there, the home, a car, and a couple of trees were completely involved.
"We had a vehicle fire that was directly as the site of the residence and that slowed down efforts to get in the structure fire," said Tom Greenwood with the Orange Cove Fire Protection District.
Two people inside the home were unable to make it out and died in the fire. Investigators from Fresno County fire are helping Orange Cove firefighters with the investigation, but at this point a cause hasn't been determined.