Objectives. To estimate impacts of COVID-19 infections and social and economic sequelae on mental and self-rated health among Latinx immigrant housecleaners in New York City. Methods. From March to June 2021, we conducted a follow-up study with 74% retention of 402 housecleaners initially surveyed before the pandemic between August 2019 and February 2020. We measured rates of self-reported COVID-19 infections, COVID-19 antibodies, and pandemic-related social and economic sequelae and examined predictors of mental and self-rated health changes using logistic regression models. Results. Fifty-three percent reported COVID-19 infections, consistent with the rate demonstrating COVID-19 antibodies. During shutdown of nonessential services, from March 22 to June 8, 2020, 29% worked as housecleaners, although this was not associated with higher COVID-19 infection rates. COVID-19-related stigma at work, lost earnings owing to COVID-19 infections, housing insecurity, food insecurity, and unsafe homes, including experiencing intimate partner verbal abuse, were statistically associated with changes in mental or self-rated health compared with prepandemic measures. Conclusions. The disproportionate impact and virtually nonexistent safety net housecleaners experienced during the first year of the pandemic highlight the importance of inclusive stopgap measures to mitigate economic insecurity and its sequelae. (Am J Public Health. 2023;113(8):893-903. https://doi.org/10.2105/AJPH.2023.307324).