This experimental paper deals with the development of a hybrid biological reactor for the treatment of a synthetic oilfield produced water under an increase in total dissolved solids (TDS) concentration. To comply with strengthening regulations concerning produced water discharge and peculiar produced water compositions, a moving bed biofilm reactor (MBBR) consisting in a combination of free activated sludge and moving biofilm supports was compared to a fixed bed hybrid biological reactor (FBHBR) consisting in a combination of free activated sludge and a fixed biofilm support. After a 216 days experimental period, the MBBR and the FBHBR were efficient to treat a synthetic produced water with chemical oxygen demand (COD) removal rate above 90% under an increase in TDS concentrations from 1.5 to 20 g·L−1. Ecotoxicity measurements on freshwater and marine microorganisms revealed an absence of toxicity on treated waters. A decrease in bacterial diversity indices with respect to the inoculum was observed in both bioreactors. This suggests that the increase in TDS concentrations caused the predominance of a low number of bacterial species.