The victim, who later died, and a man were shot for unknown reasons while seated in a parked car at the Westfield Mission Valley Mall around 1:15 a.m. PST by an unknown gunman who remained at large.
Police said they were looking for a man wearing tan slacks who was seen leaving the area. A gray Honda sedan was also being sought, KNSD-TV, San Diego, said.
Both victims were shot in the head and torso. The woman who called for help died at a hospital and the male might not survive, police told the San Diego U-T.
Homicide investigators were on the scene Tuesday morning when the mall opened for Christmas Eve shoppers.