The SkyLife air ambulance had a pilot, a nurse a paramedic and a patient aboard when it went down Thursday night, American Ambulance General Manager Todd Valeri said at a news conference.
The helicopter was headed from Porterville Municipal Airport to San Joaquin Community Hospital in Bakersfield when it crashed, Kern County fire officials said.
Officials did not say why the patient was being taken to the hospital, and the names of the dead are being withheld until family members can be informed.
The crash site was remote field on private property outside of the town of McFarland about halfway into the trip, officials said.
There was dense fog and heavy rain in the area and it wasn't clear whether it caused the crash, but "weather conditions are always a factor," Valeri said.
"This was a safe, experienced crew," he said.
The weather also made it difficult to find and reach the site, and rescue crews didn't get there for more than two hours after the helicopter went missing.
The Federal Aviation Administration and the National Transportation Safety Board will be investigating the crash, officials said.