In 2019, approximately 51 million U.S. adults aged ≥18 years reported any mental illness,* and 7.7% reported a past-year substance use disorder† (1). Although reported prevalence estimates of certain mental disorders, substance use, or substance use disorders are not generally higher among racial and ethnic minority groups, persons in these groups are often less likely to receive treatment services (1). Persistent systemic social inequities and discrimination related to living conditions and work environments, which contribute to disparities in underlying medical conditions, can further compound health problems faced by members of racial and ethnic minority groups during the coronavirus disease 2019 (COVID-19) pandemic and worsen stress and associated mental health concerns (2,3). In April and May 2020, opt-in Internet panel surveys of English-speaking U.S. adults aged ≥18 years were conducted to assess the prevalence of self-reported mental health conditions and initiation of or increases in substance use to cope with stress, psychosocial stressors, and social determinants of health. Combined prevalence estimates of current depression, initiating or increasing substance use, and suicidal thoughts/ideation were 28.6%, 18.2%, and 8.4%, respectively. Hispanic/Latino (Hispanic) adults reported a higher prevalence of psychosocial stress related to not having enough food or stable housing than did adults in other racial and ethnic groups. These estimates highlight the importance of population-level and tailored interventions for mental health promotion and mental illness prevention, substance use prevention, screening and treatment services, and increased provision of resources to address social determinants of health. How Right Now (Qué Hacer Ahora) is an evidence-based and culturally appropriate communications campaign designed to promote and strengthen the emotional well-being and resiliency of populations adversely affected by COVID-19-related stress, grief, and loss (4).