The fire happened around 7:35 a.m. at a building on the 1600-block of East Oakton Street with a business in front and a living area in the back, according to Des Plaines fire chief Alan Wax.
Firefighters found one person inside the building during a search, and a second person got out of the building before crews arrived, Wax said.
Both victims were treated on the scene and transported to Advocate Lutheran General Hospital in Park Ridge, one in fair condition and one in critical condition.
According to the fire chief, there were several animals inside the building during the fire. Several cats died and four other cats and one dog were rescued. One cat was taken to an animal hospital to be treated for smoke inhalation, while the other animals were being cared for by neighbors, according to Wax.
Businesses near the building sustained minor damage.
The cause and origin of the fire remain under investigation.
The Sun-Times Media Wire contributed to this report.