Abstract: Background and Objective: Deficiency of trace elements that are cofactors of fertilizing enzymes can cause sperm dysfunction and male infertility. In the present work, the levels of some trace metals (Cu, Zn and Mn) and the activities of hyaluronic acid degrading enzymes were evaluated in semen from fertile and infertile men. Materials and Methods: Two hundred and sixteen semen samples were divided into 5 groups: Group 1 (G1) was healthy controls and another 4 infertile group 2-5 according to WHO criteria. Levels of Cu, Zn and Mn and activities of hyaluronidase (Hase), N-acetyl-β-D-glucosaminidase (NAG) and β-D-glucuronidase (β-Gluc) were estimated in the sperms and seminal plasma of these groups. Results: Significant decreases in Cu2+ and Zn2+ contents were observed in seminal plasma and sperms homogenate of the infertile groups. Moreover, the activities of the 3 hyaluronic acid degrading enzymes in sperms homogenate supernatant of infertile males were highly reduced compared to the control group. The Hase activity in seminal plasma of all groups was completely absent. The activity of β-Gluc in seminal plasma of infertile males was highly elevated than control group. Conclusion: The disturbance in levels of trace metals and the hyaluronic acid degrading enzymes activities are associated with human male infertility and may be useful tools in predicting semen quality.