At approximately 9 p.m., the Clay County Sheriff's Department and Lewis Volunteer Fire Department were dispatched to the fire, located at 12970 S. County Road 500 W., Jasonville.
According to information provided by Sheriff Mike Heaton, the home had been abandoned.
The man was taken to Wishard Hospital via Air Evac for severe burns he received from the fire
Another male victim was transported to Union Hospital, Terre Haute. Officials said the extent of injuries to both victims was unknown.
Heaton said witnesses informed officials the second person "jumped" from a second-story window to escape the fire.
Heaton told The Times it was believed the fire started in the upstairs portion of the home.
Authorities speculated a methamphetamine lab explosion might have taken place.
Upon arrival at the scene, firefighters stated they could smell a strong chemical odor.
Heaton also said Duke Energy was called to the scene, but added there was no electricity in the home.
The names of the victims were not released.
According to Heaton, officials with the Indiana State Fire Marshal's office were scheduled to be at the scene Monday.
Other agencies responding to the scene included the Clay City Volunteer Fire Department, Jasonville Fire Department, Wright Township Fire Department and TransCare.