The fire broke out in CLogansport, some 120 kilometers north of state capital Indianapolis.
Local television WTTV reported that two adults, a mother and an adult son, were rescued from the house by law enforcement officials who first arrived on the scene. The two were taken to a nearby hospital for treatment.
Previous reports indicated that six other people, including four children aged up to 10 years old, were trapped inside the burnt two-story home, adding they could have died in the heavy fire.
In a televised press conference held Wednesday afternoon, Indiana police said they could only recovered the bodies of two adults and two children so far and the search was continuing.
During the rescue operation, fire fighters had to truck in water to battle the flames as the house is located in a rural, non-hydrated area. Fire engines arrived first were reportedly out of water within five minutes.
High winds and freezing temperatures also hindered the rescue.
Local authorities have started an investigation into the cause of the fire. Police said they could not rule out any possibility, accidental or criminal.