The blaze was reported at a home on the 300 block of East 106th Street around 10:40 p.m.
Responding crews found the man's body inside the one-story house.
"The fire was confined to the structure itself. It wasn't very large, but it was substantial enough to cause damage inside, and unfortunately appeared to take the life of the individual that was inside the home," said David Liske of the Los Angeles Fire Department.
He is the 13th person to die in a fire this year, according to LAFD spokeswoman Katherine Main.
"There was evidence of at least one smoke alarm, although it was unknown if it was operational," she said.
Neighbors were stunned to learn of the tragic incident, and said the victim worked hard to support his wife and two kids.
"He was a good, hardworking guy and took care of his family," said neighbor Reggie Kegler.
On Sunday, the fire department traveled door-to-door and handed out smoke detectors, carbon monoxide detectors, batteries and fire safety information to people in the neighborhood.
Jamie Moore of the LAFD says the department is trying to combat a spike in fire deaths by emphasizing the importance of smoke detectors.
"Two weeks ago on 50th Place, the Los Angeles Fire Department had a fatality and we went door-to-door. Out of 10 homes, we found seven homes that did not have working smoke alarms," said Moore. "It is having a direct impact in our community when our firefighters go door-to-door and they educate these individuals who live in the area about the importance of smoke alarms and making sure that they work."
The cause of the fire remains under investigation, but LAFD officials say it appears suspicious and a possible case of arson.