Under the pressure of the unprecedented economic sanctions, the Russian Federation faces the tasks of reformatting its foreign economic strategy, transforming its trade policy, changing supply chains, and expanding cooperation with the partners that maintain economic neutrality, particularly with the countries in Latin America, the Asia-Pacific region, and the Middle East. The purpose of this research is to determine to what extent economic sanctions can serve as a factor for activating trade and economic relations between Russia and the countries of MERCOSUR as the most significant potential partners from the Latin American region. The research question of the article is to what extent it is possible to sooth the impact of sanctions on the Russian economy by stimulating trade links with MERCOSUR countries. The article attempts to compare the relative significance of Brazil, Argentina, Uruguay, and Paraguay as trade and economic partners for Russia at the time of sanctions. The article identifies factors contributing to the growth of potential of mutual trade and economic cooperation and those constraining it; provides an assessment of the current development of trade and investment relations between the parties; calculates indicators to determine the possibility of substituting the lost markets for export-import operations by the new ones.