The treatment of wastewater from a cellulosic ethanol biorefinery presents special challenges. A pilot scale process that utilized a continuous stirred tank reactor (CSTR), an internal circulation reactor (IC), and a sequencing batch reactor (SBR) with ozone oxidation enhancement was developed for the treatment of this challenging biorefinery wastewater. The CSTR and IC were used for COD removal through anaerobic treatment, and the SBR process was used for nitrogen removal through alternating aerobic nitrification and anaerobic denitrification. The combined process removed 85% of chemical oxygen demand (COD) and 80% of ammonium. The corresponding effluent concentrations of COD and ammonium were 1591 +/- 226 mg/L and 61 +/- 8 mg/L, respectively. Ozonation enhanced the biodegradability of the anaerobic effluent, the BOD5/COD ratio of which increased from 0.15 +/- 0.02 to 0.33 +/- 0.05. The BOD5/COD ratio of the effluent from the SBR was 0.07 +/- 0.01, which indicated the effluent was no longer treatable using a biological process. A total sulfate removal efficiency of 65% was obtained through an alternating anaerobic and aerobic process, and the final effluent sulfate concentration was 217 +/- 10 mg/L. (C) 2016 Elsevier B.V. All rights reserved.