It happened around 10 p.m. Friday on Greylog Drive near Airport Boulevard.
Firefighters said they had difficulty entering the burning home due to burglar bars on the windows and door.
Once inside, they used a thermal-imaging camera and found a victim in the hallway. Another victim was found in the kitchen of the smoke-filled home.
One of the victims died and the other was in serious condition at a hospital.
Arson investigators were on scene looking for the cause of the fire.
The identities of the victims were not immediately released.