BackgroundAs early as before the coronavirus disease 2019 (COVID-19) pandemic, nearly one billion people worldwide suffered from mental health problems. Of all the mental health conditions, major depressive disorder (MDD) is the leading cause of global health-related burden. During the COVID-19 pandemic, many uncertain factors affecting mental health accumulated, such as virus transmission, blockade and ban, public transport restrictions, closure of schools and enterprises, and reduction of social interaction, which led to an increase in the potential risk of MDD, further increasing the global health-related burden.MethodologyTo better clarify the public interest in major depressive disorder during the COVID-19 pandemic, a Google Trends analysis was employed with data from December 2019 to December 2021, taking the cumulative diagnosis rate and cumulative mortality rate of COVID-19 as the reference standard, The changes in public interest and behavior in online searching for major depressive disorder in the three countries most affected by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus (i.e. the United States, Brazil, and India) were evaluated.ResultsWe observed that during the COVID-19 pandemic, public interest in major depressive disorder increased significantly on the Internet. At the same time, compared with the United States, this upward trend is more prominent in India and Brazil. The study found that the major depressive disorder search index of the United States reached the maximum at the end of September 2021, the major depressive disorder search index of Brazil reached the maximum at the beginning of July 2021, and the major depressive disorder search index of India reached the maximum at the beginning of June 2021. The above time nodes are the first turning point of decline after the continuous surge of COVID-19 confirmed cases in the United States, Brazil, and India, indicating that there is an important time correlation between the surge of COVID-19 cases and the public online search term major depressive disorder.ConclusionThe Google Trends analysis shows that public interest in major depressive disorder is on the rise under the COVID-19 pandemic and that COVID-19 may be associated with MDD. These findings deserve further exploration, especially as a growing body of research reports suggests that the COVID-19 pandemic has led to a surge in the prevalence of MDD. The epidemic alerts the vast majority of countries to urgently strengthen mental health systems and provide patients with the necessary interventions based on the determinants of poor mental health.