The aim of the current study was to assess relationships between multiple metals burden in human seminal plasma and semen quality parameters. Levels of five metals (lead, manganese, copper, arsenic, and selenium) in human seminal plasma were determined by inductively coupled plasma mass spectrometry (ICP-MS), and the correlations between the metal concentrations and semen parameters (sperm concentration, sperm motility rate, and sperm morphology) were analyzed. The activities of acid phosphatase (ACP) and of α-glucosidase in human seminal plasma were also determined. Of the 100 subjects, 21 had fertility problems according to the World Health Organization criteria and were designated as "abnormal group." Significant inverse correlations were found between the concentrations of Cu, As, Pb, and the sperm concentrations (r (Cu) = -0.312, P (Cu) = 0.029; r (As) = -0.328, P (As) = 0.021; r (Pb) = -0.377, P (Pb) = 0.008). Moreover, the Cu, Mn, and Se concentrations were significantly higher in the abnormal group than that in the normal group (P (Cu) = 0.024, P (Mn) = 0.002, P (Se) = 0.002). The ACP activity was significantly higher in the normal group than that in the abnormal group (P = 0.021). We also found a significantly negative correlation between α-glucosidase activity and the levels of As (r = -0.367, P = 0.023). These findings provide evidence for relationships between human semen quality and metal exposures. These relationships are consistent with animal data, but additional human and mechanistic studies are needed.