The couple, 79-year-old Cecil Knutson and 68-year-old Dianna Bedwell have not been seen or heard from since Sunday afternoon.
The missing couple's last cell-phone signal pinged them somewhere near Deer Springs Road and Interstate 15, 13 miles away from Valley View Casino.
They were last seen in their 2014 white Hyundai Sonata with California license plates, 7EHE981.
If you have any information on the couple, you are asked to call San Diego County Sheriff's Department at 858-565-5200.
CBS News 8's Matt Johnson has details and family reaction in the above video report.