Three different separation configuration options namely: pure distillation (option A), gas stripping based (option B) and liquid-liquid extraction based (option C) for separating Acetone Butanol Ethanol (ABE) fermentation broth which contains low butanol concentration in the presence of butyric and acetic acid which is a characteristic of unsuccessful switching from acidogenesis to solventogenesis process during ABE fermentation were modelled using Aspen Plus simulation software and analysed using first and second law of thermodynamics. With the consideration of heat integration, the separation efficiency achieved by the gas stripping based option and the LLE based option were approximately the same (0.0558 and 0.0571 respectively) while that of the pure distillation based option was 0.0165. The second law analysis shows that the lowest entropy generation occurs in the gas stripping separation configuration, followed by the LLE option, then the pure distillation option. From the second law analysis, it was observed that the highest irreversibility occurs in the first distillation column of the pure distillation process. This is as a result of large quantity of water contained in the fermentation broth. It was found that reducing the quantity of water contained in the fermentation broth using either gas stripping or LLE operation drastically reduces the irreversibility or entropy generation in the process. Apart from water, the presence of acetic acid in the fermentation broth also poses a challenge due to the formation of butanol- acetic acid azeotrope. From this work, it was found that the excessive use of water for dilution of fermentation substrates in order to lower substrate inhibition and the unsuccessful shift from acidogenesis to solventogenesis during ABE fermentation operation poses a major energy penalty during fermentation product purification as the energy required to successfully separate the fermentation broth is far more than the energy content of butanol product obtained. (C) 2015 Elsevier Ltd. All rights reserved.