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 H 2O 2/COD and H 2O 2/Fe 2+ molar ratios were 2.5 and 20, respectively. Under the optimum operating conditions, complete degradation of the antibiotics occurred in 1min. In the second part of this study, a bench-scale SBR was operated for 239days and fed with Fenton-treated wastewater under different operating conditions. BOD 5/COD ratio below 0.40 of the Fenton-treated wastewater had negative effect on the SBR performance. Hydraulic retention time (HRT) of 12h was found suitable for the SBR and increasing HRT to 24 and 48h did not significantly improve the SBR efficiency. Statistical analysis (two-way ANOVA) was made on the results to optimize the H 2O 2/Fe 2+ molar ratio and Fenton reaction time and it was found possible to reduce the Fe 2+ dose and increase the Fenton reaction time. Under the best operating conditions (H 2O 2/COD molar ratio 2.5, H 2O 2/Fe 2+ molar ratio 150, Fenton reaction time 120min and HRT 12h), 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. © 2011 Elsevier B.V.