The purpose of this study was to investigate the association between personal religiosity, mental health, and substance use outcomes among Black and Hispanic adults during the first six months of the COVID-19 outbreak in New York City (NYC). Phone interviews were conducted with 441 adults to obtain information on all variables. Participants self-reported race/ethnicity as Black/African American (n= 108) or Hispanic (n= 333). Logistic regression were used to examine associations between religiosity, mental health, and substance use. There was a significant inverse association of religiosity and substance use. Religious people had a lower prevalence of drinking alcohol (49.0%) compared to non-religious people (67.1%). Religious people also had substantially lower prevalence of cannabis or other drug use (9.1%) in comparison to non-religious people (31%). After adjusting for age, sex, race/ethnicity, and household income, the association of religiosity with alcohol use and with cannabis/other drug use remained statistically significant. Despite restricted access to in-person religious activities and congregational supports, the findings suggest that religiosity itself may be helpful from a public health perspective, independent of serving as a conduit for other social services.