Seminal proteins can be considered as factors that control fertilization. Clusterin is one such protein that has been implicated in many activities, including apoptosis inhibition, cell cycle control, DNA repair, and sperm maturation. In this study, the relationship between human secretory clusterin (sCLU) in seminal plasma with sperm parameters, protamine deficiency, and DNA fragmentation was investigated. Semen samples were collected from 63 Iranian men, and semen analysis was performed according to World Health Organization criteria and computer aided semen analysis (CASA). The concentration of sCLU in seminal plasma was measured by enzyme-linked immunosorbant assay (ELISA), protamine deficiency was determined by chromomycin A3 staining (CMA3 ), and sperm DNA fragmentation was checked by sperm chromatin dispersion (SCD) assay. The level of sCLU in seminal fluid of fertile patients was 48.3 ± 38.6 ng/ml and in infertile patients was 15.5 ± 9.7 ng/ml; this difference was significant (P < 0.001). sCLU correlated negatively with protamine deficiency, sperm DNA fragmentation, and abnormal morphology. In conclusion, seminal clusterin can be considered as a marker for the quick assessment of semen quality in male infertility studies.