The difference between the COSMO-RS calculated values and those from dGsolvDB3/overlap are significant. We observed that ∆G * solv (AH) calculations more negative than -10 kcal mol -1 tended to have much higher errors than those more positive. The solutes with highest error tended to have many carbon atoms and include at least one carboxylic acid site. Further tests showed this to also occur when comparing CombiSolv-QM and CombiSolv-Exp, which are separate datasets of COSMO-RS calculations and solvation energies for neutral solutes (see SI). The higher errors in this negative solvation energy regime might be due to greater difficulty in accurately measuring experimental solvation energies for those compounds, or may be from greater errors in COSMO-RS. The relative contribution of each potential source of error is currently unclear to the authors.