Firefighters took 45 minutes to control the blaze after it swept through and damaged the entire 4-storey Thai Green Guesthouse in Soi Trok Kai Jae off Phra Sumen Raod, Chana Songkram subdistrict at 6.45 am.
A foreign man suffered leg injuries after he jumped from the second floor and he also suffered burns to his chest.
The guesthouse owner, Saengrawee Satchapirak, 64, suffered from smoke inhalation and a voluntary firefighter had an electric shock from a power leakage and fell from the second floor, said Chana Songkram police.
The three injured were taken to Vajira Hospital.
The fire will be investigated by forensic science police and the Public Works Division of the Phra Nakhon district.