The mental consequences of the COVID-19 pandemic and the strict lockdown measures implemented by governments world-wide to fight it are currently unknown. We performed an online survey study in Switzerland and analyzed data acquired during confinement (wave 1) and during partial lifting of measures (partial deconfinement) (wave 2). Wave 1: Data from over 10’000 individuals living in Switzerland were collected between April 6 and 8, 2020, starting 3 weeks after the beginning of confinement. While 24.4% of the participants reported no change in stress levels, 49.6% of the participants reported an increase in stress levels during confinement as compared to the time before the COVID-19 pandemic. We identified several potential sources for people feeling more stressed during confinement, such as the burden related to changes at work or school, problems with childcare or not being able to spend more time with others. The changes in stress levels were highly correlated with changes in depressive symptoms. 57% of the participants reported an increase in depressive symptoms. Further, the prevalence of moderately severe or severe depressive symptoms (PHQ-9 score ≥ 15) increased from 3.4% before the COVID-19 pandemic to 9.1% during confinement. Interestingly, 26% of participants showed a decrease in stress level during confinement, suggesting that for those individuals the confinement involved a reduction of stressors and/or resulted in more time for recovery. Finally, we identified several behaviors amenable to change that were related to a reduced increase in stress level and depressive symptoms during confinement. Wave 2: Data from over 10’000 individuals living in Switzerland were collected between May 11 and June 1, 2020 during partial deconfinement. As for wave 1, we observed diverse reactions with regard to stress levels: While 28% of the participants reported no change in stress levels, 40% of the participants reported an increase in stress levels during partial deconfinement as compared to the time before the COVID-19 pandemic. We identified similar sources for people feeling more stressed as during confinement and the changes in stress levels were highly correlated with changes in depressive symptoms. 49.5% of the participants reported an increase in depressive symptoms. Further, the prevalence of moderately severe or severe depressive symptoms (PHQ-9 score ≥ 15) remained elevated with a prevalence rate of 11.7%. With regard to changeable behaviors during the pandemic, we found (as in wave 1) that spending more time pursuing new projects, spending more time pursuing hobbies at home, and light physical exercise were related to less stress increase.A comparison between the two waves indicated that while the waves did not substantially differ in the distributions of changes in stress levels or depressive symptoms, they did differ with regard to the distribution of anxiety ratings. Specifically, anxiety levels decreased from wave 1 to wave 2. Finally, we identified risk and resilience factors with regard to the development of depressive symptoms (present in both waves): A history of a prior psychiatric disorder was a risk factor for developing moderately severe or severe depressive symptoms during the pandemic. In a resilient group of people who had none or only minimal depressive symptoms before and during the pandemic, older people (≥ 55 years), men and individuals with no history of prior psychiatric disorder were overrepresented. Thus, advanced age, male gender and the absence of prior psychiatric disorder were identified as resilience factors.