Nine people who were related died in the three-bedroom home, Pikangikum tribal chief Dean Owen told Canada's public broadcaster CBC.
The victims were six adults and three children, he said. It wasn't clear if they were immediate or extended family members.
Police and fire fighters responded to the blaze on the Pikangikum First Nation reserve about 310 miles (500 kilometers) northwest of Thunder Bay, Ontario shortly before midnight local time Tuesday (0344 GMT Wednesday), Ontario Provincial Police Constable Diana Cole told AFP.
"A number of persons have been confirmed deceased and there are a number of persons that remain unaccounted for," she said.
The cause of the fire has yet to be determined, she added, saying police and the fire marshal's office are investigating the incident.
The impoverished remote community is accessible only by air and reportedly has one of the world's highest suicide rates.
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