Serotonin (5-HT) and inflammation are 2 major hypotheses in schizophrenia (SZ) pathogenesis, both of which involve platelets. However, the association between platelet and SZ has not been well studied. The aim of this study was to evaluate changes of platelet count (PLT), mean platelet volume (MPV), platelet-large cell ratio (P-LCR), platelet distribution width (PDW), and plateletcrit (PCT) in patients with first-episode schizophrenia (FES). Meanwhile, 3 inflammation markers, including neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and monocyte-lymphocyte ratio (MLR), were evaluated. Complete blood count of 106 FES patients, 82 first-episode depression (FED) patients, and 120 healthy controls (HCs) were compared. In addition, PLR, NLR, and MLR were calculated and compared among 3 groups. Our data suggested that PLT, MPV, P-LCR, PDW, PCT, NLR, PLR, and MLR in FES patients were significantly increased than those in the HCs ( < 0.01 or  < 0.05, respectively). PLT, PCT, PLR, and MLR in FED patients were significantly higher than those in the HCs ( < 0.01). However, no significant difference in MPV, P-LCR, and NLR was identified between FED patients and HCs ( > 0.05). Moreover, MPV, P-LCR, PDW, NLR, and MLR in FES patients were significantly higher than those in FED patients ( < 0.01 or  < 0.05, respectively). The elevation of PLT, MPV, P-LCR, PDW, PCT, NLR, PLR, and MLR in FES patients supported 5-HT and inflammation hypotheses in SZ pathogenesis. Further, our data suggested that increasing levels of MPV, P-LCR, PDW, NLR, and MLR might help to distinguish FES from FED. Clinical Trials.gov ID: 2018JJ2580.