A large body of research, most of which is ecological, has investigated the relationship between job loss or unemployment rates and mental health, substance use, and suicide. Groups historically experiencing health disparities (for example, Black and Hispanic populations and those without a high school or college degree) have been differently affected by unemployment during the COVID-19 pandemic. Similarly, preliminary evidence from three states suggests that suicide has disproportionately affected Americans who are members of racial and ethnic minority groups over the course of the pandemic. COVID-19 has affected the workforce in unique ways that differentiate the pandemic from previous economic downturns. However, previous research indicates that increases in suicide rates associated with economic downturns were driven by regional variation in unemployment, availability of unemployment benefits, and duration and magnitude of changes in unemployment. Policy mitigation strategies may have offset the potential impact of unemployment fluctuations on suicide rates during the pandemic. Policies include expanded unemployment benefits and food assistance, as well as tax credits and subsidies that reduced child care and health care costs. Research is needed to disentangle which populations experienced the most benefit when these strategies were present and which had the greatest risk when they were discontinued. Evidence-based strategies that expand the mental health workforce and integrate mental health supports into employment and training settings may be promising ways to help workers as they navigate persistent changes to workforce demands.