Rockford fire officials said they received 30 to 40 911 calls about an explosion at a home in the 2800-block of Lapey Street.
When emergency crews responded to the scene, they found a large fire inside what they described as an apartment building.
Fire officials said two of the men were thrown from the building into the front yard and were taken to the hospital for treatment. Fire officials described their injuries as serious, but gave no further details.
Another man was found under debris near the front area of the home after the fire had been put out, and was pronounced dead, fire officials said.
Fire officials said the relationship between the three victims was not yet known.
No further details about the explosion and its cause has been released.