The Tibetan Plateau, a region that hosts low to middle-latitude glaciers and a high density of metasedimentary rocks, is a hotspot of continental weathering and carbon cycling. However, quantitative estimations of sulfide oxidation and how it affects CO2 budgets from the plateau weathering are lacking. Here we use chemical and isotopic datasets from the studied small catchments in the Tibetan Plateau to estimate that 69.1% to 77.0% of stream SO42– originates from sulfide oxidation. Thus, more than 80% of the CO2 consumed by silicate weathering is counterbalanced by transient CO2 release from H2SO4-driven carbonate dissolution in the study area. In addition, the sulfide oxidation rate for glacial catchments is 5 times that of nonglacial catchments. The CO2 release rate from acid generated by sulfide oxidation in metasedimentary catchments is approximately 3 times that of granitic catchments. We propose that sulfide oxidation has greatly modified the CO2 budget of chemical weathering of the Tibetan Plateau. This study reveals new constraints on the CO2 budget in the Tibetan Plateau weathering, and will provide important insights into the carbon cycle during the plateau uplifting in Cenozoic.