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View Code? Open in Web Editor NEWSocial behaviors play a key role in the spread of COVID-19. Consequently, regional variation in personality traits that capture individual differences in these social behaviors may offer new insight into regional variation in COVID-19 cases. Here we combine self-reported personality data (N ≈ 3.5 million people), official COVID-19 prevalence rates, and behavioral observations (N ≈ 29 million people) to show that regional personality differences in the US and Germany predict the regional onset and growth of COVID-19 cases above and beyond a highly conservative set of socio-demographic, socio-economic, and pandemic-related control variables. Openness and Extraversion were consistently related to earlier COVID-19 onsets and steeper growth rates. The opposite pattern was found for Neuroticism. We also shed light on regional responses to the outbreak, showing that regional personality (i) is associated with objective indicators of regional social distancing, and (ii) predicts self-reported social distancing beyond the effects of individual-level personality.