• Affinity chromatography is a fast alternative to determine serum albumin sorption. • Evaluation of approach with respect to differences compared to standard methods. • Comparison of chromatographic approach to LSER predictions. • Application for a large dataset of environmentally relevant chemicals. Sorption to serum albumin is essential for characterizing the distribution of chemicals in organisms. It impacts the concentration of the freely dissolved chemical in vivo and in vitro , and needs to be considered when effect concentrations at the target side are derived from nominal concentrations. Sorption to serum albumin is often characterized by the serum albumin-water partition coefficient K SA/W , which is traditionally determined using dialysis experiments. However, dialysis approaches are time-consuming and require a large amount of pure protein. Thus, we investigated affinity chromatography as a fast alternative to characterize the sorption of chemicals to serum albumin. To this end, the application of two types of serum albumin columns (bovine vs. human), different temperature settings (30°C vs. 37°C), and the impact of 2-propanol as modifier in the mobile phase were evaluated. Moreover, a linear regression model was calibrated with 49 experimentally determined log K SA/W values from the literature to predict sorption to serum albumin directly from the retention factor log k HSA . In addition, we tested a prediction approach based on linear solvation energy relationships and compared the two procedures. Further, we compiled a dataset of log k HSA values for 378 chemicals, which we classified according to their ionization state and structure, and according to environmentally relevant classes like persistent, mobile, and toxic chemicals, pesticides, and plastic additives. There was no specific trend observed for particular classes of chemicals, which means that there is a demand for determining the sorption to serum albumin for these chemicals for the correction of the effect concentration in bioassays, e.g., and to assess bioaccumulation in higher tier organisms such as fish or rodents.