The coronavirus pandemic has had devastating mental health consequences across the world. Among others, economic uncertainty created by job loss due to the pandemic has been a main culprit. This study examines the deleterious effect of losing a job personally or living with a family member who did on mental health among American adults. We also examine whether this link varies across two measures of vulnerability at the individual level (low household income and ethnic minority status). We further run cross-level interaction models between job loss and two contextual moderators (COVID-19 cases and community social capital). Based on multilevel analysis of Census House Pulse Survey consisting of U.S. probability samples collected over a 10-month period between April 2020 and February 2021, we find strong support for the positive relationship between job loss and mental distress, which is more pronounced among Americans with lower household income. This relationship also increases in regions with higher average coronavirus infections but decreases in places with higher stock of social capital.