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The global pandemic COVID-19 has raised an enormous threat to the world’s health care services, economy, socio-political bodies, and infrastructure. This pandemic has negatively affected both physical and mental health. Mental well- being is more than the existence or absence of mental illness. It is an intersection between emotional, psychological, social, and physical well-being. Many persons have experienced significant mental health problems this year. Public health interventions related to COVID-19, including quarantines and lock-downs, can have a detrimental effect on people’s mental health status through environmental change, disruption of services, self, social isolation, financial uncertainty, and work loss enhanced stress. The purpose of the study was to investigate the gender differences of mental health (perceived stress, anxiety, and depression) and explored associated factors during the COVID-19 epidemic among peoples living in Alappuzha, Pathanamthitta, and Kollam district.