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Despite the global impact of COVID-19, studies comparing the effects of COVID-19 on population mental health across countries are sparse. This study aimed to compare anxiety and depression symptoms during the COVID-19 lockdown among adults from 11 countries and to examine their associations with country-level COVID-19 factors and personal COVID-19 exposure. A cross-sectional survey was conducted among adults (≥18 years) in 11 countries (Brazil, Bulgaria, China, India, Ireland, North Macedonia, Malaysia, Singapore, Spain, Turkey, United States). Mental health (anxiety, depression, resilient coping, hope) and other study data were collected between June–August 2020. Of the 13,263 participants, 62.8% were female and 51.7% were 18–34 years old. Participants living in Brazil had the highest anxiety and depression symptoms while participants living in Singapore had the lowest. Greater personal COVID-19 exposure was associated with increased anxiety and depression symptoms, but country-level COVID-19 factors were not. Higher levels of hope were associated with reduced anxiety and depression; higher levels of resilient coping were associated with reduced anxiety but not depression. Substantial variations exist in anxiety and depression symptoms across countries during the COVID-19 lockdown, with personal COVID-19 exposure being a significant risk factor. Strategies that mitigate COVID-19 exposure and enhance hope and resilience may reduce anxiety and depression during global emergencies.