Authorities responded to the 900 block of East 59th Street after the explosion sparked a fire at about 6:15 a.m. Flames were knocked down within 25 minutes, officials said, but the damage caused the building to partially collapse.
Two people working in the building were thrown into the street and one was wedged under a car and had to be freed by firefighters, but did not survive, said Eric Scott, a fire department spokesman.
Fire Capt. Stephen Ruda says a second man died at a hospital after he was hit with 34,500 volts from a downed power line. Ruda says the man was trying to move his truck away from the wreckage.
Ruda says dogs were sent in to search the building after reports that a third person might be trapped but they found nothing.
Natural gas apparently sparked the blast but the building also contained flammable oxygen and acetylene, Scott said.
The Associated Press contributed to this story.