Bio-butanol production based on ABE (acetone-butanol-ethanol) fermentation is facing increasing interest as a transport fuel, since it offers significant advantages to other bio-fuels. However, to ensure an economic operation two bottlenecks has to be overcome: (1) high cost of the fermentation substrate, and (2) high energy demand for butanol purification via distillation due to low solvent concentration in fermentation broth. While first bottleneck might be overcome by the use of alternative feedstock like lignocelluloses or agro-food-wastes, the latter can be targeted by introducing hybrid purification concepts, combining in-situ removal techniques with distillation. Experimental and literature data based on lab-scale size experiments operated with synthetical fermentation broth are used to parameterize an Aspen Plus® simulation to predict the energy demand for bio-butanol purification for three in-situ removal techniques coupled with distillation and to compare to a standalone distillation sequence: gas stripping, pervaporation and adsorption/desorption. Depending on the initial solvent content of fermentation broth, with 23.2 - 31.2 MJ/kg butanol the heat demand of the standalone distillation sequence is slightly below the energy content of butanol of about 36 MJ/kg. Applying gas-stripping and pervaporation before purification via distillation reduces the heat demand by 50 % to 13.6 - 16.8 MJ/kg and 12.0 - 14.5 MJ/kg butanol, respectively. Best result is shown by combining adsorption and distillation with an energy demand of 5.0 – 5.7 MJ/kg butanol. However, the advantageous low overall energy demand results from low efforts in the distillation step, only considering separation of butanol and water, but neglecting purification of acetone and ethanol obtained in ABE fermentation.