Climate extremes such as droughts, floods, heatwaves, frosts, and windstorms add considerable variability to the global year-to-year increase in atmospheric CO2 through their influence on terrestrial ecosystems. While the impact of droughts on terrestrial ecosystems has received considerable attention, the response to flooding events of varying intensity is poorly understood. To improve upon such understanding, the impact of the 2019 US flooding on regional CO2 vegetation fluxes is examined in the context of 2017-2018 years when such precipitation anomalies are not observed. CO2 is simulated with NASA’s Global Earth Observing System (GEOS) combined with the Low-order Flux Inversion (LoFI), where fluxes of CO2 are estimated using a suite of remote sensing measurements including greenness, night lights, and fire radiative power and bias corrected based on in situ observations. Net ecosystem exchange CO2 tracer is separated into the three regions covering the Midwest, South, and Eastern Texas and adjusted to match CO2 observations from towers located in Iowa, Mississippi, and Texas. Results indicate that for the Midwestern region consisting primarily of corn and soybeans crops, flooding contributes to a 15-25% reduction of net carbon uptake in May-September of 2019 in comparison to 2017 and 2018. These results are supported by independent reports of changes in agricultural activity. For the Southern region, comprised mainly of non-crop vegetation, net carbon uptake is enhanced in May-September of 2019 by about 10-20% in comparison to 2017 and 2018. These outcomes show the heterogeneity in effects that excess wetness can bring to diverse ecosystems.