Police responded to the Hampton Inn & Suites located near the 55 Freeway and Dyer Road around 9 a.m.
Responding officers found the children dead in a third-floor room. Police in nearby Costa Mesa had called to request that Santa Ana officers check on the childrens' welfare, Santa Ana police Cpl. Anthony Bertagna said.
A woman who has since been identified as the children's mother was found around 8 a.m. in a crashed car in Costa Mesa. Comments she made led officers to the hotel room.
Officials said the woman attempted to commit suicide by crashing her gray Honda Accord into protective poles surrounding an electrical box behind a Home Depot in the 2300 block of Harbor Boulevard.
The steel poles ultimately prevented the car from colliding into the electrical box and further hindering officers' rescue efforts.
Responding officers said the woman refused to unlock her door locks and get out of her vehicle. The driver also placed an electrical cord around her neck and began attempting to strangle herself.
Officers broke the window in an attempt to drag her out and found a propane tank inside the front passenger compartment area of the car. That is when the woman reportedly told police about her hotel room in Santa Ana and her two kids.
As paramedics were preparing to take the injured woman to a hospital, "she made some statements that indicated a crime might have occurred" in Santa Ana, Costa Mesa Sgt. Tim Starn said.
She was then transported by ambulance to Hoag Hospital in Newport Beach and booked for two counts of murder upon her release.
Her last known residence was listed as San Jose. Officials said the 42-year-old was driving a car with a Georgia license plate. It remains unknown what she was doing in Southern California.
The childrens' identities and ages were not immediately released. The cause of death was under investigation but was being treated as a homicide. Police say no weapons were recovered at the scene.
Hotel guests were stunned at the discovery at the quiet inn on a sunny weekend in Southern California.
"My goodness if there's two children involved that's just horrendous to say the least," Mike Ramey, who was staying at the hotel with his fiancee said. "As a parent, it's just a heartbreaker."
Officials obtained a warrant to search the Hampton Inn & Suites. Crime scene investigators later processed the room.
Detectives say they don't know what the woman's motive may have been for allegedly killing her kids.
Investigators are now trying to track down the children's father.
The Santa Ana Police Department was handling both crime scenes.
The Associated Press contributed to this report.