Two Chapel Hill fire trucks and one UNC truck were on hand to help extinguish the fire, which was put out in 15 to 20 minutes, officials said.
Bart Willis, assistant general manager of the shelter, said he was working in the building when he heard "the night deposit door close." After that, Willis said he heard "an explosion."
Pat Sanford, who has been director of the shelter for 15 years, said 911 officials told her there was an explosion in the night deposit box.
She said the night deposit box is used for people who want to leave injured or abandoned animals. Sanford said those animals dropped off are picked up in the morning by animal shelter officials, who would then assess and treat the animals' injuries.
Battalion Chief David Lewis said the fire was suspicious and that officials were not ruling out anything as of yet.
"(The fire) wasn't bad," he said. "I think most of the damage was superficial. It is suspicious and we are treating it as such at this time."
Fire Marshal Caprice Mellon, who will be investigating the cause of the fire with assistance from the Chapel Hill police, said exact details, such as how much damage was done and the cause of the fire, have yet to be determined.
Sanford said a boa constrictor was injured. The four animals killed during the fire were two baby squirrels, a rabbit and a ferret, she said.
But Sanford praised the Chapel Hill Fire Department for its efforts in containing the spread of the fire and smoke.
"It was very smoky inside, but the firemen did a wonderful job," she said.
"There was no severe damage to the animals except those in the wildlife room."
Sanford said the damage could have been worse if Willis had not been working.
"If he hadn't have been here, we would have lost more lives."
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