The 2D IR measurements and MD simulations support a model in which PEGylation stabilizes Gal3C by reorganizing solvent dynamics within the surrounding protein solvent shell without any measurable changes to the protein secondary structure. Neither 2D IR nor MD simulations detected evidence for PEGylation-driven desolvation of the protein surface or significant differences in the SASA among Gal3C, Gal3C-PEG 550 and Gal3C-PEG 5k. While the SASA was investigated in the present study at picosecond to nanosecond timescales, our findings align with earlier observations from NMR spectroscopy data that showed PEGylation did not alter the SASA of Gal3C over longer timescales. The present conclusions appear to differ with those from earlier computational studies and hydrogendeuterium exchange experiments that reported PEGylation reduced the conjugated protein's SASA.