The explosion happened about 6:15 p.m. at a home in the 4200 block of West 181st Avenue in unincorporated Hebron, the Lake County Sheriff's Department said.
Two men, ages 49 and 39, were taken to hospital in serious condition for burn injuries, officials said. A 64-year-old man was taken to a hospital in serious condition for other injuries from the explosion.
The home was engulfed in flames after the explosion and spread to nearby field, the sheriff said. Multiple fire departments battled the fire.
The cause of the explosion was not yet known.
The Indiana State Fire Marshal, Porter County Bomb Squad, and the Bureau of Alcohol, Tobacco and Firearms are investigating.
No further information was immediately available.