Carbon dioxide is the most important anthropogenic greenhouse gas that requires continuous monitoring of variability of its content in the atmosphere. Currently, it is carried out using different remote and local methods. Satellite-based methods allow investigating spatial and temporal variations of carbon dioxide in the vicinity of megacities that have various anthropogenic carbon dioxide sources. Moreover, they can provide information on localization of such sources and even allow estimating the intensity of their emission. We present an analysis of mesoscale spatial and temporal variations of carbon dioxide content in the vicinity of Moscow megacity in the period of 2014–2018. For the analysis, we took carbon dioxide data obtained using measurements of solar radiation in the near infrared spectral range by nadir viewing instrument onboard the OCO-2 satellite. We observe significant spatial and temporal variations of carbon dioxide in the Moscow region which are mainly caused by the presence of numerous anthropogenic sources. According to satellite data, the full amplitude of spatio-temporal variations for the carbon dioxide column-averaged dry-air mole fraction amounts to 70 ppm, exceeding by 17 % the mean values. The maximum spatial variations during one day of observations totals 50.1 ppm, exceeding by 13 %.