The role of water in stabilizing sites of protonation in small gaseous ions is investigated using electrospray ionization (ESI) coupled with infrared photodissociation spectroscopy and computational chemistry. Protonation of p-aminobenzoic acid (PABA) and p-aminobenzoic acid methyl ester (PABAOMe) occurs at the carbonyl oxygen atom both in isolation and when one water molecule is attached. However, protonation occurs at the amine nitrogen atom, which is the most favorable site in aqueous solution, for PABAOMeH(+)center dot(H2O)(3) and for a significant fraction of PABAH(+)center dot(H2O)(6). Fewer water molecules are necessary to stabilize the solution-phase isomer of PABAOMeH(+) (3) than for PABAH(+) (>= 6), indicating that the favorable hydrogen bonding in PABAH(+) is a more important factor than the higher gas-phase basicity of PABAOMeH(+) in stabilizing protonation at the carbonyl oxygen atom. Relative Gibbs free energies (133 K) calculated using B3LYP and MP2 with the 6-311++G** basis set were significantly different from each other, and both are in poor agreement with results from the experiments. omega B97X-D/6-311++G**, which includes empirical dispersion corrections, gave results that were most consistent with the experimental data. The relative stabilities of protonating at the carbonyl oxygen atom for PABAH(+)center dot(H2O)(0-6) and PABAOMeH(+)center dot(H2O)(0-2) can be rationalized by resonance delocalization. These findings provide valuable insights into the solvent interactions that stabilize the location of a charge site and the structural transitions that can occur during the ESI desolvation process.