 Head coach Chip Kelly retained Bethea and Eric Reid as the starting safety tandem to start the regular season.On September 18, 2016, Bethea recorded nine combined tackles, a pass deflection, and intercepted a pass by quarterback Cam Newton in a 45–27 loss at the Carolina Panthers in Week 2.In Week 4, he collected a season-high 12 combined tackles (11 solo) and broke up a pass during a 24–17 loss to the Baltimore Ravens.