Updated project metadata. Scarcely understood defects lead to asthenozoospermia which results in poor fertility outcomes. Incomplete knowledge of these defects hinders the development of new therapies and reliance on interventional therapies, such as in vitro fertilization, increases. Sperm cells, being transcriptionally and translationally silent, necessitate the proteomic approach to study the sperm funnction. We have performed a differential proteomics analysis of human sperm and seminal fluid and identified over 1,700 proteins. We have included 667 proteins in sperm and 430 proteins in seminal plasma dataset for further analysis. Statistical and mathematical analysis combined with pathway analysis and self organizing maps clustering and correlation was performed on the dataset. It was found that sperm proteomic signature combined with statistical analysis as opposed to the seminal plasma proteomic signature can differentiate the normozoospermic versus the asthenozoospermic sperm samples.