The inferno was reported about 4:45 a.m. at a large single-story facility near the intersection of Slauson Avenue and Soto Street. The building housed two businesses, including El Bodegon Imports, a home-goods retailer.
Nearly 100 Los Angeles County firefighters responded to the scene and were attacking the flames from aerial ladders after the building's roof collapsed. The fire sent a giant plume of thick, black smoke into the air above the surrounding area.
The intensity of the blaze initially forced firefighters to assume defensive positions, amid fears that one of the structure's walls would collapse. The Fire Department was eventually able to extinguish the flames while preventing them from spreading to nearby structures.
There were no immediate reports of injuries.
The cause of the fire is under investigation.
A witness, Miguel Zavaleta, speculated that the blaze may have began after an effort to fend off frigid temperatures overnight.
"There's a lot of homeless people around," Zavaleta told ABC7. "So I'm guessing that they tried to lit a fire for themselves and it went out of control."
Inspector Craig Little, a spokesman for the Fire Department, confirmed only that "upon arrival, their were numerous cardboard boxes leaning against the building."