BACKGROUND: Current knowledge on psychiatric illness following periods of social distancing during the COVID-19 pandemic is mostly limited to smaller studies in selected populations. This nationwide study of all 4.6 million Danish adults examined if periods of social distancing were associated with changes in surrogate measures of mental health. METHODS: All Danish adults (≥18 years) were included and rates of collection of antidepressant prescriptions, psychiatric hospital admissions, and suicide or suicide attempts for the periods March 12, 2020-May 20, 2020 (lockdown period 1), and December 21, 2020-March 1, 2021 (lockdown period 2), were compared to corresponding periods 1 year prior. Individuals were censored due to death or SARS-CoV-2 infection. RESULTS: Antidepressant consumption increased for both period 1 and period 2, with an incidence rate ratio (IRR) of 1.02 (95% CI: 1.01-1.02, CONCLUSION: Periods of social distancing during the COVID-19 pandemic were associated with an increase of antidepressant consumption, but decreased rates of psychiatric hospitalization. Suicide risk seemed increased during the second lockdown period.