The incident happened around 3 p.m. in Mill Creek near the Thurman Flats Picnic Area on Highway 38 outside of Mentone.
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The San Bernardino County Sheriff's Department said the mother was attending to her son when her daughter was taken downstream.
"The mother searched for her but could not locate her," read a statement from the sheriff's department. "When she returned, her son was missing and assumed to be down river as well."
The mother then hiked up to the picnic area and contacted another family member to help, but they couldn't find the children.
Authorities said it took the mother about an hour to call 911 due to limited cell service in the area.
Deputies from the Yucaipa Station, Sheriff's Air Rescue, Mentone Station County Fire personnel, a U.S. Forest Service Rescue Crew and SBCSD Search and Rescue members worked together in the search.
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Crews first found the girl and rushed her to a local hospital. Shortly after, they found the boy. They were both found near the river's edge, according to authorities.
The girl was sent to Redlands Community Hospital by ambulance while the boy was airlifted to Loma Linda University Medical Center.
They were pronounced dead later in the evening.
The incident remains under investigation.