Main objects for wastewater treatment operation are to maintain effluent water quality and minimize operation cost. However, the optimal operation is difficult because of the change of influent flow rate and concentrations, the nonlinear dynamics of microbiology growth rate and other environmental factors. Therefore, many wastewater treatment plants are operated for much more redundant oxygen or chemical dosing than the necessary. In this study, the optimal control scheme for dissolved oxygen (DO) is suggested to prevent over-aeration and the reduction of the electric cost in plant operation while maintaining the dissolved oxygen (DO) concentration for the metabolism of microorganisms in oxic reactor. The oxygen uptake rate (OUR) is real-time measured for the identification of influent characterization and the identification of microorganisms' oxygen requirement in oxic reactor. Optimal DO set-point needed for the micro-organism is suggested based on real-time measurement of oxygen uptake of micro-organism and the control of air blower. Therefore, both stable effluent quality and minimization of electric cost are satisfied with a suggested optimal set-point decision system by providing the necessary oxygen supply requirement to the micro-organisms coping with the variations of influent loading.