The structure of deterministically nanopatterned surfaces created using a combination of electron beam lithography and reactive ion etching was evaluated using small-angle neutron scattering (SANS). Samples exhibit 2D neutron scattering patterns that confirm the presence of ordered nanoscale cavities consistent with the targeted morphologies as well as with SEM data analysis. Comparison of SANS intensities obtained from samples in air and in contact with an aqueous phase (pure deuterium oxide, D2O, or a contrast matched mixture of D2O + H2O) reveals formation of stable gaseous nanobubbles trapped inside the cavities. The relative volume of nanobubbles depends strongly on the hydrophobicity of the cavity walls. In the case of hydrophobic surfaces, nanobubbles occupy up to 87% of the total cavity volume. The results demonstrate the high degree of sensitivity of SANS measurements for detecting and characterizing nano- and mesoscale bubbles with the volume fraction as low as ∼10–6.