The fire broke out around 11:30 p.m. on the 1200 block of South 46th Street.
Crews arrived to find heavy smoke showing from the second floor.
Officials say one person jumped from the second floor window onto a neighbor's deck.
Another person was rescued from a breezeway where they took shelter to escape the flames.
The two victims were taken to the Hospital of the University of Pennsylvania for treatment.
When firefighters got inside the home they disovered the body of a man.
The fire was placed under control within thirty minutes.
The names of the victims have not been released.
License and Inspection has been called to the scene to investigate.
Officials say there were no smoke alarms in the home and no word yet on what sparked the blaze.