The coronavirus disease 2019 (COVID-19) pandemic could disproportionately affect individuals who have a substance use disorder (SUD). However, little information exists on COVID-19-related experiences among individuals with a SUD. We examined whether individuals with a SUD differ from other individuals with regard to COVID-19 testing, susceptibility, and employment-related vulnerability. We used data from a U.S. nationally representative survey (n = 1,208). Using logistic regressions, we examined whether individuals with SUDs differ from other individuals regarding underlying health conditions, COVID-19 testing, access to paid sick leave, and loss of employment. Data were collected in late May-early June, 2020. Four percent of participants reported that a healthcare professional had told them they had a SUD. We found that, compared to those without SUDs, respondents with SUDs had higher odds of having lost their job due to the pandemic (adjusted odds ratio AOR:5.17, 95% confidence interval CI:2.28-11.74). Among individuals who were employed prior to the pandemic, people with SUDs had lower odds of having paid sick leave (AOR:0.26, 95% CI:0.09-0.74). Our study indicates that individuals with SUDs could be disproportionately affected by COVID-19 economically, which might worsen SUD and racial/ethnic health disparities.