BackgroundIndividuals with a substance use disorder (SUD) are at a significantly higher risk for coronavirus disease-19 (COVID-19) and have higher rates of COVID-19 related hospitalization and death than those without SUD. This study assessed COVID-19 vaccine trust, transmission awareness, risk and protective behaviors, and effects of COVID-19 on mental health and smoking among a sample of clients in California residential SUD treatment programs and identified factors associated with vaccine trust.MethodsA multi-site sample of SUD treatment clients (n = 265) completed a cross-sectional survey. Multivariable logistic regression was used to identify factors associated with COVID-19 vaccine trust.ResultsParticipants were predominantly male (82.3 %) and racially/ethnically diverse (33.3 % Non-Hispanic White). Most participants were aware of COVID-19 modes of transmission, however, only 39.5 % trusted a COVID-19 vaccine would be safe and effective. Factors independently associated with trust in a COVID-19 vaccine included age (AOR = 1.03, 95 % CI = 1.02, 1.05, p = 0.0001) and wearing a mask all the time (AOR = 2.48, 95 % CI = 1.86, 3.31, p = 0.0001). African Americans were less likely than White participants to trust that a COVID-19 vaccine is safe and effective (AOR = 0.41, 95 % CI = 0.23, 0.70, p = 0.001).ConclusionSUD treatment clients were aware of COVID-19 modes of transmission; however, fewer than half trusted that a COVID-19 vaccine would be safe and effective. Health communication about COVID-19 for people with SUD should use a multipronged approach to address COVID-19 vaccine mistrust and transmission risk behaviors.