Spent sulfite liquor (SSL) is a byproduct of the sulfite pulping process of wood. SSL usually contains monosugars and lignosulfonates, which are fermented to produce ethanol and dried to generate lignosulfonate salts. However, the SSL that was used in this work was derived from the first step of a 2-step sulfite pulping process of softwood under mild pulping conditions in the first stage of cooking. The resulting SSL contained polymeric hemicelluloses, which are not used today but have many potential applications. The up-concentration of this SSL had been performed on a lab scale by ultrafiltration. However, the pilot-scale ultrafiltration of hemicellulose-rich sodium-based SSL has not been reported. In this study, the operating conditions for the lab-scale concentration of hemicellulose-rich, sodium-based SSL were examined in a pilot-scale membrane filtration unit. The permeate flux and retention of products were lower in the pilot equipment compared with the lab-scale setup, perhaps related to the lower Reynolds number and shear rate in the former, as indicated by simulations of computational fluid dynamics. The pilot equipment also ran at a higher volume reduction compared with the lab-scale system, which could explain the difference in flux and retention. The effects of fouling and cleaning were also determined, wherein an alkaline cleaning step (pH 11) for 1 h was sufficient to remove foulants and maintain a stable average flux of 88 L/m2h and the nonchanging retention of products. (Less)