The blast at the two-storey building in Aliso Viejo, south of Los Angeles, also injured two people.
The explosion ripped through the first floor of the two-story medical building, blowing out walls and windows - and sending the preschool kids scattering, along with their parents.
A US official says a deadly explosion at a Southern California office building is being investigated as an intentional act and investigators believe the blast may have come from a package.
Authorities had not found an explosive device Tuesday night but were searching through debris that was left after the blast.
The FBI is responding to the scene, a law enforcement official told CBS News senior investigative producer Pat Milton. Fire officials say a third person suffered smoke inhalation.
Fire and sheriff's officials said the building appeared to be undergoing some type of renovation. She and the three injured were likely in close proximity to the explosion, Sawyer said.
There was no initial indication of terrorism, according to the Federal Bureau of Investigation.
Authorities said they are still trying to figure out what happened and wouldn't comment on whether the incident could be related to a gas leak or explosive devices.
A woman who was on her way to an appointment in the area told CBS2 she arrived just after the blast occurred, and she saw fire on the roof of the building. Initially it was reported that the vehicle crashed into the building, but later it became known that the explosion occurred inside the centre.
"Take care of my mother, take care of my mother!" shouted one woman as she fled, according to NBC4. The other woman was burned and her head was bleeding.
They said they were not actively looking for any suspects.
Fennessy says children at a daycare across the street were not injured.
Two survivors had critical injuries "that were consistent with an explosion, but not necessarily consistent with a bomb", said Carrie Braun, a spokeswoman for the Orange County Sheriff's Department.