The fire broke out late yesterday night in a timber and wood house at Yigo, in the island's north, the Guam Fire Department said.
"Our firefighters faced one of their worst fears. Five young lives were lost to a structure fire in Yigo," the department said on its Facebook page.
Fire department spokesman Kevin Reilly said five children were found dead in the property and another three survived and were taken to hospital.
He said the survivors were two boys and a girl but could not provide further details about the five fatalities. KUAM News reported they were all girls, aged three to 16.
It was not known if they were siblings.
Witnesses reported seeing flames 25-foot high engulf the house, which reportedly had no water or power and was being used for temporary accommodation.
"This probably... To claim this many lives, is the worst in our history," Reilly said.
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