PURPOSE: In oxygen-enhanced magnetic resonance imaging of the lung (O2-MRI), motion artifacts related to breathing hamper the quality of the parametric O2-maps. In this study, fully automatic non-rigid image registration was assessed as a post-processing method to improve the quality of O2-MRI. MATERIALS AND METHODS: Twenty healthy volunteers were investigated on a 1.5T MR system. O2-MRI was obtained in four coronal sections using an IR-HASTE sequence with TE/TI of 12/1200ms. Each section was repeatedly imaged during oxygen and room-air ventilation. Spatial differences among the images were corrected by fully automatic non-rigid registration. Signal variability, relative enhancement ratio between oxygen and room air images, and spatial heterogeneity of lung enhancement were assessed before and after image registration. RESULTS: Motion artifacts were corrected in 5-10s. Non-rigid registration reduced signal variability of the source images and heterogeneity of the O2-maps by 1.1±0.2% and 11.2±2.9%, respectively (p<0.0001). Registration did not influence O2 relative enhancement ratio (p=0.06). CONCLUSION: Fully automatic non-rigid image registration improves the quality of multislice oxygen-enhanced MRI of the lung.