Abstract: Recently, environmental pollution was introduced as a contributing factor in decreasing male fecundity via deterioration of semen quality. Our study aimed to compare serum and seminal plasma levels of lead and cadmium in rural versus urban infertile men from Assiut governorate and also, to detect the correlations of these heavy metals with conventional semen parameters and sperm vitality. Methodology Seventy five infertile male patients from rural areas and 84 from urban areas in Assiut governorate were included in the study. Lead and cadmium levels in serum and seminal plasma, conventional semen analysis and sperm vitality with hypo-osmotic swelling test (HOS) were evaluated in all patients. Results: There was a significant increase in both serum and seminal concentrations of lead and cadmium among infertile men from urban areas in comparison to those from rural areas. No statistically significant difference could be detected in semen parameters between the 2 groups. There were significant negative correlations between serum and seminal concentrations of lead and cadmium on one hand and normal sperm morphology, progressive motility and vitality (HOS) percentages on the other hand. Conclusions: Infertile men from urban areas are more subject to hazardous environmental toxicants as heavy metals which may help in diagnosis of the unexplained male infertility and necessitates special attention in management of those subjects attending infertility clinics and belonging to urban areas.