Bioelectrochemical systems (BES) have long been viewed as a promising wastewater treatment technology. However, in reality, the performance of bioelectrochemical systems fed with real (and therefore complex) wastewaters is often disappointing. We have sought to investigate the combined impacts of complex substrates and presence of electron acceptors. In particular, this study illustrates and systematically evaluates the disparity in performance between a BES acclimatised with acetate and those acclimatised with more complex carbohydrates (glucose, sucrose or starch) and in the presence and absence of sulphate. Relative to acetate only, operating with complex carbohydrates reduced current by 73%–87% and coulombic efficiency by 4%–50%. Acclimation with complex carbohydrates seriously impeded the colonisation anode by Geobacteraceae, resulting in substantially reduced capacity to produce current (60.2% on average). Combined acclimation with sulphate further reduced current by 35% on average, and resulted in a total reduction of 83%–93% relative to the acetate control. However, the presence of an electrogenic sulphide-sulphur shuttle meant sulphate had little effect on the coulombic efficiency of the BES. The results indicate that a reduction in current and coulombic efficiency is, at present, an unavoidable consequence of operating a BES fed with complex wastewater. Researchers, designers and policy makers should incorporate such losses in both their plans and their prognostications.