The blaze broke out at the property on Derwent Street, off Carholme Road, at about 03:30 GMT on Saturday.
Two people escaped from the house but the body of a man, who has not been named, was found after the fire was brought under control.
Lincolnshire Police said a joint investigation with the fire service had been launched into the cause of the blaze.
The body of a man has been found following a house fire in Lincoln.