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Previous research on the acute effect of antipsychotics on cytokines is inconclusive.First episode psychosis (FEP) is an ideal population to study this topic.Our meta-analysis found decreased IL-2 and IL-6 post-treatment levels in FEPOur meta-analysis found decreased IL-2 and IL-6 post-treatment levels in FEP.IL-6 and IL-2, and possibly IL-1β, could be considered as state markers.TNF-α, IL-17, and IFN-γ might represent trait markers in drug-naïve FEP.Schizophrenia is likely to be associated with immunological abnormalities. However, antipsychotics may induce immunomodulatory effects, by influencing plasma cytokines. In order to distinguish these influences, we carried out a systematic review and meta-analysis exploring the acute effect of antipsychotics on candidate cytokines plasma levels (IL-1β, IL-2, IL-6, IL-17, IFN-γ, TNF-α) among drug-naïve subjects with first episode psychosis.We searched main Electronic Databases, identifying eight studies meeting our inclusion criteria. Plasma cytokines values were used to estimate standardized mean differences. Heterogeneity across studies was evaluated using the I2 index and controlled in relevant sensitivity analyses. IL-2 (p = 0.023) and IL-6 (p = 0.012) levels showed a significant decrease after four weeks of antipsychotic treatment. Relevant sensitivity analysis confirmed these findings. IL-1β had high between-study heterogeneity. However, leaving out one study, a significant decrease after treatment was found. IL-6 and IL-2, and possibly IL-1β, could be considered state markers, decreasing after antipsychotic treatment, whilst TNF-α, IL-17, and IFN-γ might be considered trait markers. Options for novel treatments in FEP, involving cytokine-modulating agents, should be further studied.