Background The COVID-19 pandemic led to mental health fallout in the US; yet research about mental health and COVID-19 primarily rely on samples that may overlook variance in regional mental health. Indeed, between-city comparisons of mental health decline in the US may provide further insight into how the pandemic is disproportionately affecting at-risk groups. Purpose This study leverages social media and COVID-19-city infection data to measure the longitudinal (January 22- July 31, 2020) mental health effects of the COVID-19 pandemic in 20 metropolitan areas. Methods We used longitudinal VADER sentiment analysis of Twitter timelines (January-July 2020) for cohorts in 20 metropolitan areas to examine mood changes over time. We then conducted simple and multivariate Ordinary Least Squares (OLS) regressions to examine the relationship between COVID-19 infection city data, population, population density, and city demographics on sentiment across those 20 cities. Results Longitudinal sentiment tracking showed mood declines over time. The univariate OLS regression highlighted a negative linear relationship between COVID-19 city data and online sentiment (β = -.017). Residing in predominantly white cities had a protective effect against COVID-19 driven negative mood (β = .0629, p < .001). Discussion Our results reveal that metropolitan areas with larger communities of color experienced a greater subjective well-being decline than predominantly white cities, which we attribute to clinical and socioeconomic correlates that place communities of color at greater risk of COVID-19. Conclusion The COVID-19 pandemic is a driver of declining US mood in 20 metropolitan cities. Other factors, including social unrest and local demographics, may compound and exacerbate mental health outlook in racially diverse cities.