The aim of the present study was to perform an exergy-based multi-objective fuzzy optimization of a continuous photobioreactor applied for biohydrogen production from syngas via the water-gas shift reaction by Rhodospirillum rubrum. For this purpose, the conventional and innovative fuzzy optimization techniques coupled with multilayer perceptron (MLP) neural model to optimize the main exergetic performance parameters of the photobioreactor. The MLP neural model was applied to correlate three dependent variables (rational and process exergy efficiencies and normalized exergy destruction) with two independent variables (syngas flow rate and agitation speed). The developed MLP model was then interfaced with three different multi-objective fuzzy optimization systems with independent, interdependent, and locally modified interdependent objectives. The optimization process was aimed at maximizing the rational exergy and process efficiencies, while minimizing the normalized exergy destruction, simultaneously. Generally, the innovative locally modified interdependent objectives fuzzy system showed a better optimization capabilities compared with the other two fuzzy systems. Accordingly, the optimal syngas photo-fermentation for biohydrogen production in the continuous bioreactor corresponded to the agitation speed of 383.34 rpm and syngas flow rate of 13.35 mL/min in order to achieve the normalized exergy destruction of 1.56, rational exergy efficiency of 85.65%, and process exergy efficiency of 21.66%. (C) 2016 Elsevier Ltd. All rights reserved.