Water is the liquid of life thanks to its three-dimensional adaptive hydrogen (H)-bond network. Confinement of this network may lead to dramatic structural changes influencing chemical and physical transformations. Although confinement effects occur on a < 1 nm length scale, the upper length scale limit is unknown. Here, we investigate 3D-confinement over lengths scales ranging from 58-140 nm. By confining water in zwitterionic liposomes of different sizes and measuring the change in H bond network conformation using second harmonic scattering (SHS), we determined long-range confinement effects in light and heavy water. D2O displays no detectable 3D-confinement effects < 58 nm (< 3 x 10(6) D2O molecules). H2O is distinctly different. The vesicle enclosed inner H-bond network has a different conformation compared to the outside network and the SHS response scales with the volume of the confining space. H2O displays confinement effects over distances > 100 nm (> 2 x 10(7) H2O molecules).