The 3-alarm fire was reported around 2:45 a.m. at 1920 Walbert Avenue in South Whitehall Township.
One of the victims was identified as 43-year-old Russell Hutchinson. He was rushed to the hospital after the fire but died a short time later.
Coroner Scott Grim said authorities are looking for Hutchinson's next-of-kin. Anyone with information is asked to call 610.782.3426.
The identity of the second man has not yet been released.
An autopsy will be conducted on both men to determine the exactly cause of death.
There was no immediate word on what caused the fire.
A Pennsylvania State Police fire marshal is assisting the South Whitehall Township police and fire departments with the investigation, as is routine with fires that involve fatalities.
However, Grim said the fire doesn't appear suspicious.