Detoxification is required for sugar bioconversion and hydrolyzate valorization within the biorefining concept for biofuel or bio-product production. In this work, the spent sulfite liquor, which is the main residue provided from a pulp mill, has been detoxified. Evaporation, overliming, ionic exchange resins, and adsorption with activated carbon or black carbon were considered to separate the sugars from the inhibitors in the lignocellulosic residue. Effectiveness in terms of total and individual inhibitor removals, sugar losses and sugar-to-inhibitor removal ratio was determined. The best results were found using the cation exchange Dowex 50WX2 resin in series with the anion exchange Amberlite IRA-96 resin, which resulted in sugar losses of 24.2% with inhibitor removal of 71.3% of lignosulfonates, 84.8% of phenolics, 82.2% acetic acid, and 100% of furfurals. Apart from exchange resins, the results of evaporation, overliming, adsorption with activated carbon and adsorption with black carbon led to total inhibitor removals of 8.6%, 44.9%, 33.6% and 47.6%, respectively. Finally, some fermentation scenarios were proposed in order to evaluate the most suitable technique or combination of techniques that should be implemented in every case.