Aim: To investigate the prevalence of high levels of sperm DNA damage among men from infertile couples with both normal and abnormal standard semen parameters. Methods: A total of 350 men from infertile couples were assessed. Standard semen analysis and sperm chromatin structure assay (SCSA) were carried out. Results: Ninety-seven men (28% of the whole study group) had a DNA fragmentation index (DFI) > 20%, and 43 men (12%) had a DFI > 30%. In the group of men with abnormal semen parameters (n = 224), 35% had a DFI > 20%, and 16% had a DFI > 30%, whereas these numbers were 15% and 5%, respectively, in the group of men with normal semen parameters (n = 126). Men with low sperm motility and abnormal morphology had significantly higher odds ratios (ORs) for having a DFI > 20% (4.0 for motility and 1.9 for morphology) and DFI > 30% (6.2 for motility and 2.8 for morphology) compared with men with normal sperm motility and morphology. Conclusion: In almost one-third of unselected men from infertile couples, the DFI exceeded the level of 20% above which, according to previous studies, the in vivo fertility is reduced. A significant proportion of men with otherwise normal semen parameters also had high sperm DNA damage levels. Thus, the SCSA test could add to explaining causes of infertility in cases where semen analysis has not shown any deviation from the norm. We also recommend running the SCSA test to choose the appropriate assisted reproductive technique (ART).