To assess the feasibility of 3D oxygen-enhanced (OE) MRI of the lung at 1.5T using multi-volumetric ultra-fast balanced steady-state free precession (ufSSFP) acquisitions. Isotropic imaging of the lung for OE-MRI was performed with an adapted 3D ufSSFP sequence using five breath-hold acquisitions ranging from functional residual capacity to tidal inspiration under both normoxic (room air) and hyperoxic (100% O2 ) gas conditions. For each O2 concentration, a sponge model (which captures the parenchymal signal intensity variation as a function of the lung volume) was fitted to the acquired multi-volumetric datasets after semiautomatic lung segmentation and deformable image registration. From the retrieved model parameters, 3D oxygen-enhancement maps were calculated. For OE ufSSFP imaging, the maximum parenchymal signal is observed for flip angles around 23° under both normoxic and hyperoxic conditions. It is found that the sponge model accurately describes parenchymal signal at different breathing positions, thereby mitigating the confounding bias in the estimated oxygen enhancement from residual density modulations. From the model, an average lung oxygen enhancement of 7.0% ± 0.3% was found in the healthy volunteers, and the oxygen-enhancement maps indicate a ventral to dorsal gravitation-related gradient. The study demonstrates the feasibility of whole-lung OE-MRI from multi-volumetric ufSSFP in healthy volunteers. Magn Reson Med 79:246-255, 2018. © 2017 International Society for Magnetic Resonance in Medicine.