Objectives: to evaluate cannabinoid receptors (CBRs) expression on peripheral immune cells, i.e., blood monocytes, neutrophils, lymphocytes, and NK cells, and their relationship to a wide range of serum cytokine levels in subjects with schizophrenia and controls. Methods: A sample of 55 people with chronic schizophrenia and 48 controls were enrolled in the study. The expression of the cannabinoid receptors CB1R and CB2R was evaluated in peripheral blood leukocytes by flow cytometry. Serum levels of cytokinesichemokines were simultaneously analyzed by cytometric bead array. Results: We found higher expression of cannabinoid receptors on cells of the innate immune system in subjects with schizophrenia when compared with controls. Serum levels of interleukin-4 (IL-4), IL-6, IL-10, IL-17, interferon (IFN-y), and (C-X-C motif) ligand 10/interferon gamma-induced protein 10 (CXCL10/ IP10) were decreased, while levels of the chemokine (C-C motif) ligand 2/monocyte chemoattractant protein-1 (CCL2/MCP-1) were increased in the schizophrenia group in comparison with controls. Patients with schizophrenia showed simpler correlation network between cytokines and CBRs expression than controls. Conclusion: Patients with schizophrenia showed increased CBRs expression in cells of the innate immune system and simpler correlation network between cytokines and CBRs expression when compared with controls. These results suggest a defective endocannabinoid system-mediated immunomodulation in patients with schizophrenia. (C) 2016 Elsevier Ltd. All rights reserved.