BACKGROUND: Positive associations between the risk of schizophrenia and the level of white blood cells (WBC) count have been suggested by observational studies. However, the causality of this association is still unclear. METHODS: We used a group of bidirectional two-sample Mendelian randomization (MR) analyses to estimate the causal relationship between schizophrenia and WBC count traits (i.e., WBC count, lymphocyte count, neutrophil count, basophil count, eosinophil count, and monocyte count). The threshold of FDR-adjusted P < 0.05 was considered as showing potential evidence of a causal effect. Instrument variables were included based on the genome-wide significance threshold (P < 5 × 10- 8) and linkage disequilibrium (LD) clumping (r2 < 0.01). In total, 81, 95, 85, 87, 76, and 83 schizophrenia-related single nucleotide polymorphisms (SNPs) were used as genetic instruments from Psychiatric Genomics Consortium for six WBC count traits, respectively. And in reverse MR analysis, 458, 206, 408, 468, 473, and 390 variants extracted from six WBC count traits were utilized as genetic instruments, which were obtained from a recent large-scale Genome-Wide Association Study (GWAS). RESULTS: Genetically predicted schizophrenia was positively associated with the level of WBC count [odds ratio (OR) 1.017, 95% confidence interval (CI) 1.008-1.026; P = 7.53 × 10- 4], basophil count (OR 1.014, 95%CI 1.005-1.022; P = 0.002), eosinophil count (OR 1.021, 95%CI 1.011-1.031; P = 2.77 × 10- 4), monocyte count (OR 1.018, 95%CI 1.009-1.027; P = 4.60 × 10- 4), lymphocyte count (OR 1.021, 95%CI 1.012-1.030; P = 4.51 × 10- 5), and neutrophil count (OR 1.013, 95%CI 1.005-1.022; P = 0.004). WBC count traits are not associated with the risk of schizophrenia in our reverse MR results. CONCLUSION: Schizophrenia is associated with elevated levels of WBC count (i.e., higher WBC count, lymphocyte count, neutrophil count, basophil count, eosinophil count, and monocyte count).