The anthropogenic impact is a major factor of climate change, which is highest in industrial regions and modern megacities. Megacities are a significant source of emissions of various substances into the atmosphere, including CO2 which is the most important anthropogenic greenhouse gas. In 2019 and 2020, the mobile experiment EMME (Emission Monitoring Mobile Experiment) was carried out on the territory of St Petersburg which is the second-largest industrial city in Russia with a population of more than 5 million people. In 2020, several measurement data sets were obtained during the lockdown period caused by the COVID-19 (COronaVIrus Disease of 2019) pandemic. One of the goals of EMME was to evaluate the CO2 emission from the St Petersburg agglomeration. Previously, the CO2 area flux has been obtained from the data of the EMME-2019 experiment using the mass balance approach. The value of the CO2 area flux for St Petersburg has been estimated as being 89±28gktgkm-2gyr-1, which is 3 times higher than the corresponding value reported in the official municipal inventory. The present study is focused on the derivation of the integral CO2 emission from St Petersburg by coupling the results of the EMME observational campaigns of 2019 and 2020 and the HYSPLIT (HYbrid Single-Particle Lagrangian Integrated Trajectories) model. The ODIAC (Open-Data Inventory for Anthropogenic CO2) database is used as the source of the a priori information on the CO2 emissions for the territory of St Petersburg. The most important finding of the present study, based on the analysis of two observational campaigns, is a significantly higher CO2 emission from the megacity of St Petersburg compared to the data of municipal inventory, i.e. g1/475800±5400gktgyr-1 for 2019 and g1/468400±7100gktgyr-1 for 2020 versus g1/430000gktgyr-1 reported by official inventory. The comparison of the CO2 emissions obtained during the COVID-19 lockdown period in 2020 to the results obtained during the same period of 2019 demonstrated the decrease in emissions of 10g% or 7400gktgyr-1.