This study evaluated the association between pus cells and semen parameters in infertile Pakistani males. Methods: A cross-sectional descriptive study was carried out in the Department of Reproductive Physiology/Health, National Institute of Health, Islamabad, Pakistan, from 2004 to 2009. A total of 1,521 subjects were analysed, along with 97 proven fathers as controls. Results: The mean of pus cells was 7.43 ± 0.43, 4.35 ± 0.34, and 4.26 ± 0.17 per high field in teratozoospermic, oligoasthenozoospermic, and asthenozoospermic groups, respectively, while it was 3.25 ± 0.26, 3.10 ± 0.19, and 2.98 ± 0.04 per high field in azoospermic, oligozoospermic and the proven father groups, respectively. The fewest pus cells were observed among proven fathers, which varied non-significantly (P >0.05) with all cases, except with teratozoospermic, oligozoospermic, and oligoasthenozoospermic cases. Pus cells showed an inverse relationship to sperm motility and count, except in azoospemia cases. Similarly, the fewest pus cells were observed among groups where normal forms where significantly more frequent (P <0.05). More pus cells were observed in cases where motility, and concentration or morphology was compromised. Similarly, low pus cell counts were seen in cases where sperm had the fewest head and neck defects. All kinds of sperm defects varied non-significantly (P >0.05) between proven fathers and normal concentration cases. Conclusion: High pus cell counts were observed in various subclasses of infertile patients. Ignorance of this pyospermic factor will make pyospermic patients to be misdiagnosed as normozoospermic. Therefore, the presence of pyospermia must be considered by physicians as a male infertility factor.