The man was the sole occupant of a two-bedroom house at 13115 Neptune Drive, where a fire was reported around 4:55 a.m.
Arriving crews saw heavy smoke and fire coming from the home's front door and window, fire spokeswoman Aisha Knowles said.
Before crews arrived at the house, neighbors tried to help put out the blaze with a garden hose and an extinguisher, Knowles said.
The man was pronounced dead at San Leandro Hospital.
Firefighters were able to knock down the blaze in about 20 minutes.
An investigation into what caused the fire is underway.