Police were examining the scene and investigating the cause of the fire at Thuy Duong Hotel on Tan Ky Tan Quy Street in Tan Son Nhi Ward.
The blaze broke out early in the morning and quickly spread, sending thick smoke through the building. Local residents tried unsuccessfully to put out the fire.
Fire and rescue police deployed fire engines and personnel to the scene, while local police cordoned off the area and managed traffic to support firefighting operations.
The fire was brought under control within minutes. Police later found a 24-year-old man dead in a rear corridor of the hotel.
A 20-year-old woman from Hue was found dead in a room on the ground floor. Both victims were guests at the hotel.
Their bodies were taken to a morgue for post-mortem examinations as police continued to investigate the cause of the fire.
During the operation, rescuers guided and evacuated 26 people from the hotel to safety.