Crews responded to the fire at 1413 East Third Street at approximately 1:30 p.m. and found the one-and-a-half story wood-framed house engulfed in flames.
Sabrina Skaggs and her boyfriend Ray Bauer had escaped the fire, the two children the woman served as caregiver for were still inside.
Bauer attempted to go after the two children before crews arrived but the conditions were too intense and he was forced out after attempting to go in multiple times.
A neighbor eventually had to pull Bauer out of the flames.
Maysville Fire Chief Eric Bach told the newspaper that both children were found dead in the kitchen.
"We had to make entry from the rear of the home, which was where the kitchen was located, because the front of the house was already fully involved," he said.
The chief said the fire may have originated in the living room, but that is currently undetermined.
The cause of the fire is under investigation.
