The regenerative free radical scavenging activity of cerium oxide (CeO2) nanoparticles was improved by tuning its microstructure via nitrogen doping (N-doping). Commercially available CeO2 (60 m(2)/g) and high-surface-area CeO2 (synthesized in-house; 220 m(2)/g) were doped with nitrogen by annealing in a nitrogen rich atmosphere. The evolution of CeO2 microstructure in Nitrogen doped (N-doped) commercial CeO2 (20 m(2)/g) and N-doped high-surface-area CeO2 (90 m(2)/g) was studied. XPS and Raman measurements revealed that N-doping of CeO2 enhanced Ce3+ surface concentration and concomitantly increased surface non-stoichiometry (surface oxygen vacancy concentration). XRD analysis of the doped samples confirmed that the nitrogen atom replaced the oxygen atom in the CeO2 lattice, yielding a lower electron density region around the N-doped sites. The high-surface-area CeO2 and its N-doped version had significantly larger lattice parameters than that of commercial CeO2 and its doped version. XAS studies revealed that the N-doped high-surface-area CeO2 had more Ce3+ active clusters than its counterparts, and effectively retained its active Ce3+ active clusters upon exposure to reactive oxygen species (ROS). To confirm, the regenerative ROS (hydroxyl radical) scavenging ability of N-doped CeO2 nanoparticles within the polymer electrolyte membrane (PEM) of an operating polymer electrolyte fuel cell (PEFC) was evaluated using in-situ fluorescence spectroscopy. The N-doped high-surface-area CeO2 showed at least 100 hours of efficient and quantitative ROS scavenging under harsh conditions - a 15-fold improvement over previous reports. This study unequivocally demonstrates that N-doping increases both the number of Ce3+ active clusters in the lattice and the Ce-O bond distance; these structural attributes enhance regenerative ROS scavenging activity of CeO2. (C) 2013 The Electrochemical Society.