The aim of this research is to show that vulnerability to pandemics is unequal across nations, and that culture besides other national factors helps unleash some of the disparities. A nation’s vulnerability to pandemics is defined as a state of fragility and dereliction at the national level perceptible at the early stage of the emergence of a pathogen when no definite information is available about it and no clear response is in place, creating a dependence on national factors as well as contextual factors. That is, vulnerability reflects the evolution or spread of a nascent pandemic in a given nation. A set of hypotheses that prescribe how a nation’s factors would contribute to its vulnerability is developed. Data reflecting the national factors of a sample of countries that reported early COVID-19 cases were collected from secondary sources to test the hypotheses. The results show that, whereas factors such as economy and healthcare had a modest effect, two cultural factors were salient in shaping a nation’s vulnerability to COVID-19. Furthermore, poverty prevalence associated with a nation’s vulnerability. Delineating how a nation’s culture and macroenvironmental factors shape its vulnerability at early stages of pandemic evolution, the results encourage policymakers to extend timely support to nations high on uncertainty avoidance and low on indulgence, as well as where poverty is prevalent. Such nations require proactive measures such as behavioral interventions and communications that are culturally sensitive and inclusive.