Jessica Barrymore, 47, daughter of actor John Drew Barrymore, died in National City, south of San Diego, on Tuesday, two days before her birthday, the coroner said.
A San Diego television station reported that she worked at a local pet store.
Drew Barrymore, 39, the star of films "Scream" and "Charlie's Angels," said she did not know her half-sister well.
"Although I only met her briefly, I wish her and her loved ones as much peace as possible and I'm so incredibly sorry for their loss," Barrymore said in a statement.
San Diego's ABC TV-affiliate KGTV reported that Barrymore's body was found by a local woman who said the car was blocking her driveway and dozens of pills were scattered on the vehicle's passenger seat.
The coroner's office planned to conduct an autopsy to determine cause of death on Wednesday.
The Barrymores' father, the son of early Hollywood star John Barrymore, was married several times. He died in 2004.