A comprehensive approach was applied to investigate oscillatory CO oxidation over a Pt/Al2O3-based diesel oxidation catalyst with small Pt particles (about 1.5 nm diameter) in a fixed-bed microreactor under relevant reaction conditions by combining spatially and time-resolved operando X-ray absorption spectroscopy, infrared thermography, and online mass spectrometry. The catalyst-bed zone responsible for the oscillatory behavior and the emerging hot spot was identified by means of IR thermography. Oscillations of the Pt oxidation state and the hot spot region evolved simultaneously and moved from the end toward the beginning of the catalyst bed with increasing reaction temperature. The changes in CO oxidation activity during oscillations can be unambiguously correlated with dynamic structural changes of the Pt particles. The applied operando approach is complementary to surface science studies and also studies on model Pt particles. Surface oxidation of small Pt nanoparticles leads to a fast deactivation of the catalyst, which is regenerated in a slow reduction step. The presence of metallic Pt is required for high activity of the catalyst.