摘要:The use of marijuana is highly prevalent among young men who have sex with men (YMSM). Past work has also shown that inflammation is elevated among YMSM, independent of HIV status. Here, we aim to examine the relationship between marijuana use and inflammation among this high-risk cohort, relative to use of other substances. Data were collected among YMSM aged 16–29 in Chicago. Multiplex cytokine and inflammatory biomarker assays were run on plasma from all persons living with HIV (PLWH) (n = 195) and a subset of HIV-negative participants (n = 489). Bivariate analyses and multivariable models assessed relationships between various substances and inflammatory biomarkers. Models were stratified by HIV status and adjusted for demographic characteristics. Most participants reported use of marijuana in the past 30 days (416, 60.8%). Mean blood C-reactive protein (CRP) levels were above the upper limit of normal (3.0 mg/L), indicative of increased risk for cardiovascular disease (mean CRP was 3.9 mg/L; SD = 8.5). In adjusted, stratified analyses, CRP was significantly lower among participants reporting frequent marijuana use (≥ 6 times per month), relative to those reporting never using marijuana, (β = − 0.38; 95% CI: − 0.73, − 0.03). However, this was entirely accounted for by an association among the HIV-negative participants and there was no significant association between marijuana use and blood CRP level among the PLWH. In summary, YMSM had markedly elevated marijuana use and blood CRP levels. Frequent marijuana use was associated with lower inflammation among only those not diagnosed with HIV. Further research is needed to explicate why there are differences between HIV-negative participants and PLWH and to leverage this information to characterize biological mechanisms by which marijuana decreases inflammation.