The children, aged between four and 11, were believed to have been killed at the remote property at Llangammarch Wells, central Wales, yesterday.
"Based on current information available to us, we are working on the hypothesis that 1 adult male and 5 children, aged between 11 and 4 years old, are unaccounted for and believed to be deceased within the house," said Jon Cummins from Dyfed-Powys Police.
"Due to the severity of damage at the scene we are unable at this stage to identify any of the deceased.
Police are currently treating the cause of the fire as unexplained.
A neighbour raised the alarm shortly after midnight on Monday, with locals naming the homeowner as David Cuthbertson, according to media reports.
Flowers and tributes have been left near the gutted farmhouse.