Solvation of perfluorooctanoic acid (PFOA) in methanol–water mixed solvents was investigated by means of the mass spectrometric analyses of clusters in the solutions. The observed clusters were composed of PFOA, methanol, and water molecules. The molecular composition of the clusters showed that PFOA was preferentially solvated by methanol in the methanol–water mixed solvents, and that the ratio of methanol molecules in the PFOA solvation sphere was beyond 0.6 at the bulk methanol mole fraction (x MeOH ) = 0.045. The microscopic environment of PFOA was almost occupied by the methanol from such lower x MeOH (x MeOH ≥ 0.045), and hence the ratio of methanol in the PFOA solvation sphere did not change at x MeOH ≥ 0.045 as much as the bulk x MeOH . This preferential solvation of PFOA by methanol suggested a potential overestimation on the dissociation constant (pK a ) of PFOA extrapolated from a Yasuda–Shedlovsky plot.