Crews responded to the Venice Hotel in the 8600 block of Venice Blvd. at approximately 2 a.m. as both of the hotel's floors were burning, according to the Los Angeles Fire Department.
Once crews arrived to the scene, they encountered heavy fire in the first floor and smoke on the second. Firefighters saw residents attempting to escape, with some even breaking windows to get out.
"The outside of my door was in flames. As soon as I opened it, literally 'poof!' Flames got into my face," said Jemal Faruki, who jumped out of the window.
One man died, and two people -- a man and a woman -- were initially hospitalized in grave condition, officials said. The conditions of those two survivors were later upgraded to serious.
Two other males were in critical and fair condition, respectively, the LAFD said. Another male suffered a minor injury and declined to be taken to a medical center.
About 105 firefighters responded to the blaze, including one who was evaluated for a respiratory issue that was not life-threatening.
Firefighters knocked down the flames in approximately 39 minutes. Captain Branden Silverman said the fire was "likely due to a space heater that was in close proximity to some combustible materials."
Arson units are investigating and Los Angeles police will assist.