ObjectiveTo investigate the factors associated with serious psychological distress (SPD) during the COVID-19 pandemic in Japan.DesignNationwide cross-sectional study using survey data.SettingInternet survey using sampling weights for national estimates conducted between 25 August and 30 September 2020 in Japan.ExposuresDemographics (age, gender), socioeconomic status (income level, employment type, educational attainment, marital status, family composition and caregiving burden); the experience of domestic violence (DV), the state of emergency and fear of and stigma related to COVID-19.Main outcome measuresPrevalence of SPD, defined as Kessler 6 Scale score ≥13.ResultsAmong 25 482 respondents, 10.0% met the criteria of SPD. Overall, women (adjusted OR (aOR) 1.59; 95% CI 1.17 to 2.16; p=0.003), ages 15–29 (aOR 2.35 compared with ages 45–59 years; 95% CI 1.64 to 3.38; p<0.001), low-income level (aOR 1.70 compared with intermediate income; 95% CI 1.16 to 2.49; p=0.007), providing caregiving to family members (aOR 5.48; 95% CI 3.51 to 8.56; p<0.001), experiencing DV (aOR 5.72; 95% CI 3.81 to 8.59; p<0.001) and fear of COVID-19 (aOR 1.96; 95% CI 1.55 to 2.48; p<0.001) were associated with SPD. Among women aged 15–29 years, who have a higher risk of suicide during the COVID-19 pandemic in Japan, caregiving, DV, fear of COVID-19 and COVID-19-related stigma were associated with SPD.ConclusionsEconomic situation, caregiving burden, DV and fear of COVID-19 were independently associated with SPD during the COVID-19 pandemic. Among young women, similar factors, except economic situation, were associated with SPD. Targeted interventions based on age and gender may be more effective in mitigating the negative impact of the COVID-19 pandemic on the population’s mental health.