The COVID-19 pandemic has had negative physical and psychological impacts worldwide. However, there has been a lack of real-world evidence concerning the predictors of severe psychological distress (SPD) among the general population in Japan during the COVID-19 pandemic. The aim of this study was to examine predictors of SPD during the COVID-19 pandemic. We investigated the predictors of new-onset SPD in the general Japanese population using data from a large-scale internet-based cohort study. We included 16 489 study participants (age range = 16-81, mean age = 52.7, percentage of male = 50%) in the analysis. Over the course of 1 year from baseline, the estimated proportion of participants who experienced SPD was 5.2% with inverse probability weighting. The predictors of SPD included younger age, being never married, being unemployed, having a higher education background, scoring higher on the Fear of Coronavirus-19 Scale, experiencing more adverse childhood experiences, reporting poorer subjective health status, and COVID-19 with oxygen therapy. Our internet-based survey of the Japanese population may have selection bias, limiting the generalizability to other countries and cultures. This study revealed that being afflicted with COVID-19 requiring oxygen therapy is the most significant predictor of SPD. In addition, we found that vulnerability to social isolation, such as never being unmarried, anxiety toward COVID-19, and susceptibility to stress, are predictors of the emergence of SPD. Therefore, the implementation of online support systems and ensuring access to accurate information may protect against SPD during the COVID-19 pandemic in Japan.