We examine the relationship between individuals’ political orientations and their compliance with and attitudes towards COVID-19 prevention measures using a Dutch nationally representative online sample. Due to ideological differences, we predict that people with left-wing and progressive orientations will comply more with and have more favourable attitudes towards COVID-19 prevention measures than people with right-wing, populist, and conservative orientations, while right-wing extremists will have lowest levels of compliance and least favourable attitudes towards prevention measures. Our results support these predictions. Furthermore, we test the effect of individuals’ economic precarity and demographic characteristics on compliance and attitudes towards prevention measures. Results show that people experiencing economic difficulties do comply yet have less favourable attitudes towards the measures, while fear of economic loss is related to both lower compliance and less favourable attitudes towards measures. Older citizens have higher levels of compliance and more positive attitudes, whereas gender and education are not consistently related to compliance and attitudes. We further explore how these three sets of factors (political orientation, economic precarity, and demographics) are related to policy preferences for either reducing infection rates or reducing the economic impact of the pandemic. Our results suggest that all three sets of predictors are important in shaping measure compliance as well as attitudes and policy support and should all be considered for a comprehensive understanding of individuals’ responses to COVID-19 measures.