The fire broke out around 12:45 a.m. on the 2000 block of South 57th Street.
Fire crews arrived to heavy flames showing on the second floor of a house.
Officials say a young boy suffered burns over 60 percent of his body.
He was taken, along with an infant child, to Children's Hospital in critical condition.
The infant was checked out for smoke inhalation and is stable.
An adult man suffered burns to his feet.
The fire was placed under control around 1:00 a.m.
So far, there is no word on what sparked the blaze.