The atomic-scale hydration structure around the 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) headgroup in a chloroform/water solution has been investigated using neutron diffraction enhanced by isotopic substitution and NMR, coupled with empirical potential structure refinement and molecular dynamics simulations. The results obtained show the preferential binding sites for water molecules on the DOPE headgroups, with the most predominant interactions being with the ammonium and phosphate groups. Interestingly, the level of hydration, as well as the association of DOPE molecules, varies according to the simulation method used. The results here suggest the presence of a tight water network around these lipid headgroups that could affect the permeability of the membrane for lipid-mediated diffusion.