The pressure, temperature, and timing (P-T-t) conditions at which CO2 was produced during the Himalayan prograde metamorphism have been constrained, focusing on the most abundant calc-silicate rock type in the Himalaya. A detailed petrological modeling of a clinopyroxene+scapolite+K-feldspar+plagioclase+quartz±calcite calc-silicate rock allowed the identification and full characterization – for the first time – of different metamorphic reactions leading to the simultaneous growth of titanite and CO2 production. The results of thermometric determinations (Zr-in-Ttn thermometry) and U-Pb geochronological analyses suggest that, in the studied lithology, most titanite grains grew during two nearly consecutive episodes of titanite formation: a near-peak event at 730–740°C, 10kbar, 30–26Ma, and a peak event at 740–765°C, 10.5kbar, 25–20Ma. Both episodes of titanite growth are correlated with specific CO2-producing reactions and constrain the timing, duration and P-T conditions of the main CO2-producing events, as well as the amounts of CO2 produced (1.4–1.8wt% of CO2). A first-order extrapolation of such CO2 amounts to the orogen scale provides metamorphic CO2 fluxes ranging between 1.4 and 19.4Mt/yr; these values are of the same order of magnitude as the present-day CO2 fluxes degassed from spring waters located along the Main Central Thrust. We suggest that these metamorphic CO2 fluxes should be considered in any future attempts of estimating the global budget of non-volcanic carbon fluxes from the lithosphere.