Firefighters, police and ambulance crews were called to the property in Hollington Old Lane, St Leonards, at 02:00 BST.
The man was recovered from the house but was later pronounced dead, Sussex Police said.
An investigation is being carried out by East Sussex Fire and Rescue and police but the cause of the blaze is not being treated as suspicious.

A new reporting procedure, changes to the way users block others and new ways of dealing with reported tweets are among the changes outlined by the social network.
Twitter told Newsbeat the changes would give users "more control over their experience".
The changes come after several high profile cases of abuse.
Twitter's head of public policy in Europe, Sinead McSweeney said: "We've always said that users' safety is a priority. It's a job that we never regard as done."
The social network said the changes will take effect gradually "in the coming weeks".
A more "mobile-friendly" process will be introduced, with users asked for less information when they first report abuse.
Twitter claims the process will make it "simpler" to flag tweets and accounts for review.
Users will also be able to report abuse which is not directly targeted at them.
"It's more intuitive, it's conversational and it gives people an opportunity to flag content which they regard as abusive, but may not be directed at them," said Ms McSweeney.
There will be a new page giving details of accounts a user has blocked.
"If you block somebody, they will no longer be able to see your profile," Ms McSweeney explained.
She added the network itself would continue to suspend users temporarily or permanently where necessary.
Twitter said it has implemented several "behind the scenes" changes to the way it handles reports from users.
There will be "more staff and more resources" and "better tools and systems" for dealing with abusive content.
Ms McSweeney suggested users could expect a quicker response to certain types of reports.
"We are constantly working to reduce the times in which it takes us to get to reports."
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A man has died in a fire on the first floor of a house in East Sussex.
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Twitter is making changes aimed at allowing users to report abuse or offensive content more easily.