ABSTRACT Background People experiencing homelessness (PEH) are vulnerable to COVID-19 transmission due to substance use, congregate living conditions, and underlying medical conditions. Yet, little is known about factors impacting drug use disorder among PEH during COVID-19 pandemic. The purpose of this study was to identify correlates associated with substance use disorder among PEH, both those who were diagnosed with COVID-19 and those who tested negative or never tested. Methods A cross-sectional, structured survey was administered to PEH (N = 102) who were recruited from sheltered and unsheltered settings. Descriptive analysis, t-tests, Fisher’s exact test or chi-squared test, and bivariate and multiple linear regression were conducted. Results PEH with a COVID-19 diagnosis included male gender, and Latino race/ethnicity (p < .05). Moreover, substance use disorder scores (p - .037) and days on the street were negatively associated with COVID-19 (p < .001). Multivariable analyses revealed a significant positive relationship between days slept on the street and substance use disorder (p < .001), and a significant negative relationship with alcohol use (p < .05); COVID-19 remained negatively associated with substance use disorder, but it was not significant. Conclusions This study provides evidence about correlates of drug use disorder among PEH. More studies are needed to understand successful individual and system-level strategies for reducing drug-related problems during COVID-19.