Nd2CuO[Formula: see text] is known to possess either oxygen vacancies or interstitial oxygen defects, depending on the synthesis route, as well as may exhibit the A-site deficiency. In this work, insight into physicochemical properties of Nd2CuO[Formula: see text] and Nd[Formula: see text]CuO[Formula: see text] layered oxides is given, focusing on the crystal structure, electrical conductivity, and oxygen permeation, as well as on numerical density functional theory (DFT) simulations concerning ionic defects formation and their possible movement in the crystal structure. The results indicate that in oxidizing conditions at low temperatures, interstitial oxygen defects are stable, but with the increase of temperature, the release of oxygen is observed, leading to formation of the oxygen vacancies. Both materials are stable at elevated temperatures in air and Ar. Larger oxygen nonstoichiometry and improved electrical conductivity at high temperatures for Nd[Formula: see text]CuO[Formula: see text] compound are accompanied by the recorded oxygen flux of ca. 0.2[Formula: see text]mL[Formula: see text]cm[Formula: see text][Formula: see text]min[Formula: see text] at 880∘C for 0.8[Formula: see text]mm thick ceramic membrane.