A growing number of case reports cite serious health complications linked to the cocaine adulterant, levamisole and women are disproportionately affected; however, the clinical effects are not well established. Between April and October of 2010, we conducted a cross-sectional study among 222 homeless and unstably housed women (116 human immunodeficiency virus [HIV]-infected and 106 HIV-uninfected). Immune markers and behavioral factors were compared in separate models by cocaine and levamisole exposure. Overall, 63% of participants were toxicology positive for cocaine/benzoylecgonine, 85% of whom also tested positive for levamisole. Differences in immune markers did not reach levels of significance among HIV-uninfected persons. Compared to HIV-infected persons who were negative for both cocaine and levamisole, the adjusted odds of low white blood cell count were significantly higher among HIV-infected persons positive for both ( p = 0.03), but not for those positive for cocaine only. Neutrophil count and HIV viral load did not differ by cocaine and levamisole status among HIV-infected persons. In a separate model, the adjusted odds of testing positive for levamisole were higher among African American women compared to Caucasian and Asian women ( p = 0.02). In the context of high levamisole prevalence, results suggest that decreased immune function as a result of levamisole exposure occurs mainly in individuals who are already immune compromised (e.g., HIV-positive), and race/ethnicity appears to be an important factor in understanding levamisole exposure among cocaine-using women. While larger and geographically diverse studies are needed to elucidate these initial findings, results suggest that levamisole may be one mechanism of immune dysfunction in HIV-infected cocaine-using women.