Chronic alcohol use induces innate immune genes, which activate the innate immune system. Neuroimmune regulatory proteins [e.g., Cluster of Differentiation 200 (CD200)] are immune response regulators and are involved in balancing the immune response. This study aimed to investigate the expression of CD200 on the surface of peripheral blood leukocytes in patients with alcohol use disorder and compare them with controls. Fifty male patients with alcohol use disorder were included in the study. A baseline assessment was done, and alcohol use history, craving, and withdrawal scores were collected. A 2-mL venous blood sample was collected from cases and controls for immunophenotyping of CD200. The control group consisted of 50 participants with similar socio-economic backgrounds. The cellular expression of CD200 on total leukocytes (median ± IQR) [39.94 (28.85, 50.01)] in cases was significantly lower compared to controls [45.07 (37.70, 51.69)] (U = 896, p = 0.015). Expression of CD200 on lymphocytes in cases was negatively correlated with years of heavy drinking and this was statistically significant (r = −0.321, p = 0.023). The study indicates that cellular expression of CD200 on the surface of peripheral blood leukocytes is reduced in alcohol-dependent patients. This reduction can contribute to exaggerated immune activity, release of pro-inflammatory cytokines, chronic microglial activation, neuroinflammation, and neurodegeneration in alcohol dependence.