Emergency services were called to the fire in Gonhill, Swansea at around 1.20pm on Saturday.
A three-year-old boy died in the fire and a 51-year-old man has also this morning been confirmed to have died in the blaze.
A 13-year-old girl and a 39-year-old woman were treated for smoke inhalation.
Detective Inspector Carl Price, from South Wales Police, said: “Our thoughts remain with the family and friends of the young boy who sadly died at a house fire in West Cross, Swansea.
“An investigation is continuing to establish the exact circumstances of the fire.
“We wish to acknowledge the efforts of the local community for the support being offered and provided to the family following this tragic incident.”
The cause of the fire, which was contained to one property, is unknown at this stage and a joint investigation is being carried out by police and the fire service.
