Oxidation generates multiple diverse post-translational modifications resulting in changes in protein structure and function associated with a wide range of diseases. Of these modifications, carbonylations have often been used as hallmarks of oxidative damage. However, accumulating evidence supports the hypothesis that other oxidation products may be quantitatively more important under physiological conditions. To address this issue, we have developed a holistic mass spectrometry-based approach for the simultaneous identification, localization, and quantification of a broad range of oxidative modifications based on so-called "dependent peptides". The strategy involves unrestricted database searches with rigorous filtering focusing on oxidative modifications. The approach was applied to bovine serum albumin and human serum proteins subjected to metal ion-catalyzed oxidation, resulting in the identification of a wide range of different oxidative modifications. The most common modification in the oxidized samples is hydroxylation, but carbonylation, decarboxylation, and dihydroxylation are also abundant, while carbonylation showed the largest increase in abundance relative to nonoxidized samples. Site-specific localization of modified residues reveals several "oxidation hotspots" showing high levels of modification occupancy, including specific histidine, tryptophan, methionine, glutamate, and aspartate residues. The majority of the modifications, however, occur at low occupancy levels on a diversity of side chains.