Introduction:The immune functions could be altered due to the exposure to heavy metals. Although the impact of heavy metals on the immune system among human populations is poorly understood, however, several recent studies illustrated the immunological changes due to human exposure to Aluminum (Al) and Lead (Pb). Aim of Work: to study the alteration in some cellular and humoral immune components among some Egyptian Al smelter workers. Materials and Methods: The studied group was composed of 55 exposed male workers in Al smelter and a matched control group of 55 administrative subjects. Full medical and occupational histories, clinical examination, and laboratory investigations including (levels of serum Al, blood Pb, serum neopterin, TNF-α, IL-2, C3, C4, IgM, IgG, total IgE, and count of CD4+ and CD8+ T-lymphocytes) were performed for the Al smelter's workers and their matched controls. Results: Clinically, the exposed smelter workers showed a significant prevalence of some manifestations as allergy, inflammation, and infections, when compared with the control group. Besides, significantly elevated levels of Al, Pb, neopterin, total IgE, and CD8+ T-lymphocytes count in addition to significantly diminished levels of TNF-α, IL-2, C3, C4, IgM, IgG, and CD4+ T-lymphocytes count were detected among the exposed group compared to their controls. Moreover, all the investigated immune parameters were significantly correlated to the duration /years of employment and the levels of both studied heavy metals in the exposed smelter's workers. Moreover, the neopterin levels were significantly correlated with the parameters of cellular immunity (CD4+, CD8+ cells, and cytokines). Conclusion: There was a significant alteration in the cellular and humoral immune functions among the smelter workers occupationally exposed to Al and Pb. Additionally; neopterin could be considered a significant biomarker for the response of cell-mediated immunity.