The application of an integrated process configuration comprising of an ion exchange (IX) column and an upflow anaerobic sludge blanket (UASB) bioreactor for the simultaneous removal of SO42- and total Se from synthetic mine wastewater was evaluated. Use of an IX column as a pre-treatment (not as post-treatment) to the UASB bioreactor gave the best overall removal performance. The combined treatment reduced the total Se and SO42- concentration from 8.0 and 1441 mg/L to 0.2 and 28.0 mg/L, respectively. This study demonstrated for the first time that an IX process as a pre-treatment to a biological process can significantly improve the oxyanion removal efficiency and the overall treatment of Se-laden wastewaters.