The fire broke out inside the Fairmount Avenue home just before 6 p.m.
With heavy flames shooting through the roof, firefighters pulled out the two residents, who were rushed to Trinitas Hospital, where they succumbed to their injuries.
Two firefighters were treated at the hospital for injuries.
One firefighter's turnout gear was burned while attempting the rescue.
Neither of the injuries were life threatening.
Firefighters were hampered by weather conditions, but they were able to contain the flames to one house.
The cause of the fire is under investigation.
Firefighters monitored the blaze all night, putting out hot spots.