We investigate the effect of culture on COVID-19 spread using a sample of 67 countries over the first 10 months of the pandemic. We find that individualistic countries have higher number of COVID-19 cases, an effect that is independent from formal institutions. A two-ways interaction effects, however, between formal institutions and individualism, shows that effective political institutions, sound governance, and better economic conditions reduce the effect on individualism on CVODI-19 spread. Our findings provide evidence that are useful not only for explaining differences in COVID-19 spread between countries but can also enable policymakers and organizations to understand what generally determines individuals’ compliance with formal rules and regulations.