The fire was reported on Clay Street between Cherry and Maple Streets.
A firefighter was also injured while responding to the scene.
"Once they got in the fire rolled over them, knocked one over the porch area. That's where the firefighter got burned. He was transported, he should be OK," SFFD Deputy Chief of Operations Mark Gonzales said.
The cause of the fire is under investigation.
An older couple was trapped in their third story bedroom overnight in San Francisco while their home was on fire. The man was killed and the woman is in critical condition. The home is on Clay between Maple and Cherry. pic.twitter.com/GE0yNsksZ6— Amy Hollyfield (@amyhollyfield) December 24, 2018