All four men, ranging in age from 18 to 20, hanged themselves in closets with belts suspended from clothing bars. They were found clothed and in a squatting position on the floor, said county coroner Jim Brimhall.
The sheriff's department believes the four were acquainted and says there is no evidence of foul play. Investigators are talking to relatives and friends to find out why the men committed suicide.
Only one left a note, and Brimhall declined to discuss its contents.
"We may never find out why," Sheriff's Lt. Ryan Holder said. "We're going to do what we can to make sure it doesn't happen again."
The four were from the Pemiscot County communities of Caruthersville and Hayti. Authorities declined to release their names. Three deaths occurred in Pemiscot County. The fourth was in nearby Scott County, where Sheriff Rick Walter said the case was unrelated. But Pemiscot County authorities say they see similarities.
The first death was in July, the most recent Nov. 10. One served as a pallbearer at another's funeral, Brimhall said.
"It's just tearing everybody in the community up," Brimhall said. "These kids, they have a little problem, but they think it's a big problem. It's a big problem to them."
Pemiscot County leaders have told young people help is available if they feel depressed or overwhelmed. The communities are also seeking help from mental health professionals.
About a third of Pemiscot County's 20,000 residents live below the poverty line. It is in southeastern Missouri's Bootheel region, so named for the shape of its boundaries.