There are concerns about acute and long-term mental health effects of the COVID-19 pandemic. This study examined the prevalence and predictors of psychological distress before, during, and after a pandemic wave in Switzerland, 2021. Prevalence of psychological distress was estimated in adults aged 35-96 years using the General Health Questionnaire-12 administered in June 2021 (Specchio-COVID19 cohort, N = 3965), and compared to values from 2003 to 2006 (CoLaus|PsyCoLaus cohort, N = 5667). Anxiety and depression were assessed from February to June 2021 using the Generalised Anxiety Disorder scale-2 and the Patient Health Questionnaire-2, respectively. Prevalence of psychological distress in June 2021, after the pandemic wave (16.0% [95% CI, 14.6%-17.4%]) was comparable to pre-pandemic levels (15.1% [14.0%-16.2%]). Anxiety and depression were highest at the start of the pandemic wave in February 2021, and declined from February to June with the relaxation of measures. Predictors of psychological distress included being younger, female, a single parent, unemployed, a change in working hours or job loss in the past 6 months, greater perceived severity and contagiousness of COVID-19, and self-reported post COVID-19. By June 2021, following a pandemic wave, prevalence of psychological distress in Switzerland was closer to pre-pandemic levels. These findings highlight the need for additional mental health support during times of stricter government policies relating to COVID-19; yet they also suggest that individuals can adapt relatively quickly to the changing context.