This paper presents a two-level hierarchical control structure for biological wastewater treatment plants, with the goal of improving effluent quality and reducing operational costs. The Benchmark Simulation Model No. 1 is used as working scenario. The hierarchical structure allows to adjust the dissolved oxygen in the fifth tank (S-O,S-5) according with the working conditions, instead of keeping it in a fixed value. Model Predictive Control (MPC) with inlet flow rate feedforward control (MPC + FF) is proposed for the lower level to control nitrate nitrogen concentration of the second tank and S-O,S-5 MPC, Affine Function and fuzzy controller are tested for the higher level to adjust the S-O,S-5 set point of the lower level based on the ammonium and ammonia nitrogen concentration in the fifth tank. Modifying the tuning parameters of the higher level, a tuning region is determined, in which the effluent quality and operational costs are simultaneously improved. (C) 2015 Elsevier Ltd. All rights reserved.