In this study, a moving bed biofilm reactor was used for biodesulfuruization using CO as the sole carbon substrate. The effect of hydraulic retention time (HRT), sulfate loading rate and CO loading rate on sulfate and CO removal was examined. At 72, 48 and 24 h HRT, the sulfate removal was 93.5%, 91.9% and 80.1%, respectively. An increase in the sulfate loading reduced the sulfate reduction efficiency, which, however, was improved by increasing the CO flow rate into the MBBR. Best results in terms of sulfate reduction (>80%) were obtained for low inlet sulfate and high CO loading conditions. The CO utilization was very high at 85% throughout the study, except during the last phase of the continuous bioreactor operation it was around 70%. An artificial neural network based model was successfully developed and optimized to accurately predict the bioreactor performance in terms of both sulfate reduction and CO utilization. Overall, this study showed an excellent potential of the moving bed biofilm bioreactor for efficient sulfate reduction even under high loading conditions.