Introduction Background Following the emergence of severe acute respiratory coronavirus 2 (SARS-CoV-2) and coronavirus disease 2019 (COVID-19), in the absence of a safe and effective vaccine, governments worldwide implemented nonpharmaceutical interventions as mitigation policies, including stay-at-home orders and nonessential business closures. Questions Were there changes to sleep, behavior, and mental health in the acute phase of the COVID-19 pandemic and its mitigation? Are there differences in regions with high versus low SARS-CoV-2 prevalence? The COVID-19 Outbreak Public Evaluation (COPE) Initiative The COPE Initiative was launched in April 2020 to assess public attitudes, behaviors, and beliefs about COVID-19 and its mitigation in the general public, and to evaluate potential mental and behavioral health consequences of the pandemic and its mitigation. Methods Sampling Frame During April 2-8, 2020, Internet-based surveys were administered through Qualtrics, LLC to adults aged ≥18 years in four cohorts (target n): Nationwide United States (U.S.; n=3010), Nationwide Australia (AU; n=1531), Citywide (N.Y.; n=507), and Citywide Los Angeles (L.A.; n=525). Quota sampling was employed to improve sample representativeness by age, gender, and race/ethnicity (U.S.) or ancestry (AU) based on Census population estimates. During June 24-30, 2020, a second wave was administered in the U.S. (n=5412), with participants reinvited from April and new contacts. Survey Instrument Respondents provided demographic information and completed questions about sleep and behavioral changes during COVID-19. Respondents also completed screeners for adverse mental health symptoms, including the 4-item Patient Health Questionnaire, 6-item Impact of Event Scale, and answered questions about substance use and suicidal thoughts. Ethics Approval & Participant Consent The Monash University Human Research Ethics Committee reviewed and approved the study protocol (#24036). This activity was also reviewed by the U.S. Centers for Disease Control and Prevention (C.D.C.) and was conducted consistent with applicable federal law and C.D.C. policy. All participants provided electronic informed consent prior to enrollment in the study. Conclusions We found that moderate to extreme disruptions were widely reported by respondents in cities and nations with both high and low prevalences of SARS-CoV-2. Time on screens increased and time spent outdoors decreased. Moderate to extreme disruptions of social life were reported by 3 in 4 respondents, while such disruptions to sleep patterns were reported by 4 in 10 respondents. We also found that prevalences of adverse mental and behavioral health symptoms reported by U.S. adults were considerably elevated compared with pre-pandemic estimates. The prevalences of anxiety and depressive disorder symptoms were 3- and 4-times higher than those reported in the second quarter of 2019 (25.5% vs 8.1% and 24.3% vs 6.5%, respectively). The percentage of respondents who seriously thought about trying to kill themselves in the prior 30 days was also elevated, with approximately two-times as many respondents reported suicidal thoughts compared with 2018 (10.7% vs 4.3%). The pandemic and its mitigation have been associated with widespread disruption to many aspects of life and have also been associated with markedly increased prevalences of adverse mental health symptoms, including suicidal ideation.