Despite the devastating impacts of the COVID-19 pandemic, it provided the opportunity to investigate factors associated with compliance with public health measures that could inform responses to future pandemics. We analysed cross-country data (k = 121, N = 15,740) collected one year into the COVID-19 pandemic to investigate factors related to compliance with COVID-19 guidelines. These factors include social norms, moral values, trust, stress, and demographic factors. We found that social norms to follow preventive measures were positively correlated with compliance with local prevention guidelines. Compliance was also predicted by concern about the moral value of harm and care, trust in government and the scientific community, stress, and demographic factors. Finally, we discuss country-level differences in the associations between predictors and compliance. Overall, results indicate that the harm/care dimension of moral foundations and trust are critical to the development of programs and policies aimed at increasing compliance with measures to reduce the spread of disease.