 On October 22, 2015, Bethea made five combined tackles before exiting a 20-3 loss to the Seattle Seahawks in the third quarter with an injury.The following day, the San Francisco 49ers placed him on injured reserve with a torn pectoral muscle.Bethea finished the 2015 season with a total of 44 combined tackles (32 solo), two passes defensed, and an interception in seven games and seven starts.