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Serotonergic psychedelics are promising treatments for neuropsychiatric disorders, and their immunomodulatory effects may contribute to their clinical efficacy. However, we lack a systematic review and meta-analysis of these effects across in vitro, in vivo non-human, and human studies. We systematically searched PubMed, EMBASE, Web of Science, PsycINFO, LILACS and ClinicalTrials.gov for all studies, published from database inception through February 9th, 2026, examining changes in immune markers after serotonergic psychedelic exposure, and meta-analyzed eligible studies. Of 9,195 studies screened, 61 studies met eligibility criteria for systematic review including 24 in vitro studies, 30 non-human in vivo studies, and seven human studies including data from 10 separate human trials. Results of the systematic review indicated that most in vitro (19/24) and non-human in vivo (25/30) studies reported anti-inflammatory effects of psychedelics. Human results were mixed with anti-inflammatory effects observed in 3/10 trials. Results of the meta-analysis of 18 eligible in vivo murine studies showed a significant decrease in proinflammatory cytokines in inflammatory models (standardized mean difference (SMD = -1.23, 95% CI [-1.54, -0.92]), but no significant effects in healthy murines (SMD = -0.06, 95% CI [-0.54, 0.43]), following treatment with a serotonergic psychedelic. Four human studies were eligible for meta-analysis; however, the small number of studies resulted in imprecise estimates and limited interpretability. Thus, while serotonergic psychedelics reduce proinflammatory cytokines in preclinical models of increased baseline inflammation, limited human evidence precludes conclusions about their translational potential.