The article analyzes the causes, implementation strategy, and results of vaccine diplomacy of the People’s Republic of China and the Russian Federation in Central and Eastern Europe. In particular, the activities of China and Russia in Serbia, Hungary, Northern Macedonia, Montenegro, Bosnia and Herzegovina, Albania, Moldova, Belarus, and Ukraine are covered. The main directions, tools, and consequences of the activation of the two states in the region are outlined. The article underlines that China is expanding its strategic goals according to the One Belt One Road Initiative through the so-called Health Silk Road, providing a vaccine to low- and middle-income countries. The goals of the Russian Federation are established more in the geopolitical and political spheres. Russia seeks to reduce the influence of the EU and the US in the CEE region from political, economic, and security perspectives. China and Russia are both allies and competitors. The two countries are trying to gain additional leverage in the CEE region by means of political lobbying, investment, finance, propaganda, Euroscepticism, public opinion manipulation, and soft power. For some time, the shortage of medicine for vaccination, which was caused by giving priority to the population of vaccine-producing countries, contributed to a rather increased activity of the PRC and the Russian Federation in the implementation of the strategy of gaining image benefits.