The first part of this study examined the effect of operating conditions on Fenton pretreatment of an antibiotic wastewater containing amoxicillin and cloxacillin. The optimum H2O2/COD and H2O2/Fe2+ molar ratios were 2.5 and 20, respectively. Under the optimum operating conditions, complete degradation of the antibiotics occurred in 1 min. In the second part of this study, a bench-scale SBR was operated for 239 days and fed with Fenton-treated wastewater under different operating conditions. BOD5/COD ratio below 0.40 of the Fenton-treated wastewater had negative effect on the SBR performance. Hydraulic retention time (HRT) of 12 h was found suitable for the SBR and increasing HRT to 24 and 48 h did not significantly improve the SBR efficiency. Statistical analysis (two-way ANOVA) was made on the results to optimize the H2O2/Fe2+ molar ratio and Fenton reaction time and it was found possible to reduce the Fe' dose and increase the Fenton reaction time. Under the best operating conditions (H2O2/COD molar ratio 2.5, H2O2/Fe2+ molar ratio 150, Fenton reaction time 120 min and HRT 12 h), the combined Fenton-SBR process efficiency was 89% for sCOD removal and the SBR effluent met the discharge standards. Combined Fenton-SBR is a feasible process for antibiotic wastewater treatment. (C) 2011 Elsevier B.V. All rights reserved.