This work proposes a biorefinery concept for brewers' spent grain where, in contrast to existing concepts, water-soluble components are separated by pressing. Subsequently, the obtained liquid is used for lactic acid fermentation with Lactobacillus delbrueckii subsp. lactis. The structural carbohydrates of the residue are converted into fermentable sugars by hydrothermal and enzymatic pretreatments. Lower amounts of inhibitory compounds for microbial growth are observed after the removal of soluble components than without removal.