Background: Xylazine is harmful to humans and detected in the United States fentanyl supply and sometimes in stimulants. Awareness of xylazine among people who use stimulants (PWUS) is underexplored. Methods: In 2023, 59 PWUS in Brockton, Massachusetts, were surveyed about their past 30-day substance use and xylazine awareness. A purposive sub-sample of 21 survey participants completed an in-depth interview, of which 18 discussed xylazine. Chi-square tests assessed global differences in demographics by xylazine awareness. Qualitative data were thematically analyzed by whether participants knew what xylazine was (i.e., xylazine awareness) and past-30-day opioid use – a proxy for xylazine exposure Results: Twenty-one (35.6%) participants were unaware of xylazine. A greater percentage of Hispanic (58.3%, n = 7), Black non-Hispanic (50%, n = 7), and Native American non-Hispanic (100%, n = 2) participants were unaware of xylazine than White, non-Hispanic participants (17.2%, n = 5) (p < 0.05). A greater percentage of participants with less education were unaware of xylazine (62.5%, n = 10) compared to participants with a high school degree or GED equivalent (37.5%, n = 9), or some college education (10.5%, n = 2) (p < 0.05). Interviews indicated limited xylazine knowledge among those only using stimulants. Participants who intended to use fentanyl but experienced deleterious effects of xylazine, including skin wounds and unexpected sedation, realized post-exposure that xylazine was the likely cause of their adverse use experiences. Conclusion: Differences in xylazine awareness by substance use, race, and education indicate a need to create literacy-appropriate, culturally relevant xylazine harm reduction messages that are communicated to PWUS by trusted messengers within diverse communities.