Lignocellulosic biomass potentially represents a great feedstock for biofuel production, but its’ pretreatment needs to be enhanced in order to make biorefineries competitive with fossil fuel based alternatives. One way to make biorefineries more economically viable is to recover and valorize all generated by-products during the biomass pretreatment step. The main goal of this original research is to design an optimal process for recovering valuable by-products after hot-liquid water pretreatment of poplar biomass. Rigorous models for all operations included in the recovery process are developed using Aspen Plus as a CAPE tool. An optimal downstream processing sequence, consisting of multiple distillation steps, is designed to recover several valuable components, such as acetic acid, formic acid, furfural and 5-hydroxymethylfurfural (HMF).