A model 2 nm Pt/TiO2 catalyst was prepared to study its CO oxidation performance. Operando diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) and online CO analysis revealed that volatile organic compounds (VOCs) present in sintering flue gas, such as CH4, C3H8, benzene, and aniline, inhibit CO oxidation over Pt/TiO2 and poison the catalyst under high weight hourly space velocity (WHSV) conditions at 150 ℃. These VOCs increased the T90 of CO conversion from 120 to 160 ℃ and caused irreversible catalyst deactivation under high WHSV at 150 ℃. A thorough analysis of operando DRIFT spectra indicates that the deactivation resulted from competitive adsorption, reactive m-CO32− prevention, and deposition of incomplete oxidation species derived from benzene rings. The deposited poisoning by-products were identified as quinone/ketone, maleate, and formate/acetate. Although the CO conversion rate recovering at high reaction temperatures, the intrinsic activity of the deactivated Pt/TiO2 catalyst was not fully restored. This work provides new perspectives for designing stable low-temperature CO oxidation catalysts in sintering flue gas.