All four were apparently shot to death, and the shooter or shooters remained at large, the Bartholomew County Sheriff's Office said.
"Several agencies are following up all leads at this time. We're working around the clock and will continue to do so until we can bring those responsible to justice," Bartholomew County Sheriff Mark Gorbett told reporters. The sheriff declined to take questions.
When Daniel Burton, 27, returned to his home in Waynesville on Saturday night, he found two men lying in the living room, apparently shot, the sheriff's office said in a statement.
When Burton could not enter his mother's bedroom, he called 911.
Police arrived and discovered a third body in the living room, and after forcing open a bedroom door, found Katherine Burton, 53, shot in her bed, the statement said.
The Bartholomew County coroner spelled the woman's first name as Kathrn.
The sheriff's office identified the three dead men as Thomas Smith, 39; Aaron Cross 41; and Shawn Burton, 41, who was no relation to the other Burtons. All were listed as from Columbus, Indiana.
Smith was believed to be the live-in companion of Katherine Burton, Coroner Larry Fisher said.
Smith was a former Marine, according to his uncle, Jack Haesely.
"We have our own theories (about what happened) but have been asked not to say anything about it," said Jayla Haesely, who said he was Smith's cousin.
Waynesville is in southern Bartholomew County, about 50 miles south of Indianapolis.