We evaluated the impact of the coronavirus disease (COVID-19) on the sex work industry and assessed how it has impacted the health and social conditions of sex workers in Singapore. We conducted a sequential exploratory mixed methods study amidst the COVID-19 pandemic from April to October 2020, including in-depth interviews with 24 stakeholders from the sex work industry and surveyor-administered structured surveys with 171 sex workers. COVID-19 had a substantial impact on sex workers' income. The illegality of sex work, stigma, and the lack of work documentation were cited as exclusionary factors for access to alternative jobs or government relief. Sex workers had experienced an increase in food insecurity (57.3%), housing insecurity (32.8%), and sexual compromise (8.2%), as well as a decrease in access to medical services (16.4%). Being transgender female was positively associated with increased food insecurity (aPR = 1.23, 95% CI [1.08, 1.41]), housing insecurity (aPR = 1.28, 95% CI [1.03, 1.60]), and decreased access to medical services (aPR = 1.74, 95% CI [1.23, 2.46]); being a venue-based sex worker was positively associated with increased food insecurity (aPR = 1.46, 95% CI [1.00, 2.13]), and being a non-Singaporean citizen or permanent resident was positively associated with increased housing insecurity (aPR = 2.59, 95% CI [1.73, 3.85]). Our findings suggest that COVID-19 has led to a loss of income for sex workers, greater food and housing insecurity, increased sexual compromise, and reduced access to medical services for sex workers. A lack of access to government relief among sex workers exacerbated such conditions. Efforts to address such population health inequities should be implemented.