Male infertility is distressingly common, with 1 in 20 Australian men currently suffering from infertility issues. The majority of sub-fertile men still produce sufficient numbers of sperm for fertilisation but the functionality of these cells is somehow compromised. Despite the relatively poor understanding of the underlying origins of many sperm defects, oxidative stress, which is exceedingly common in the infertile male cohort, is not only highly linked with the onset of DNA damage but also drives the loss of sperm function. Therefore, oxidative stress has a central role in mediating poor sperm quality. Our investigation of defective sperm function has identified HSPA2, a molecular chaperone that is responsible for facilitating the expression of an oocyte-receptor complex on the sperm surface and thus fertilisation in our species. We have also shown that products of oxidative stress, including reactive aldehydes, have the ability to adduct HSPA2, and consequently lead to the loss of oocyte recognition. The molecular descriptions of how oxidative stress is induced in the male germline and how this leads to loss of oocyte recognition is the focus of this investigation. We have used a combination of mass spectroscopy and molecular modelling approaches to study the structure of HSPA2 and further, to identify the molecular mechanisms that result in disruption of the oocyte-receptor complex. Our data has revealed that under a state of oxidative stress, the adduction pattern of HSPA2 leads to perturbation of specific structural elements that are critical for the chaperoning activity of the protein. This is consistent with the demonstration that HSPA2 adduction disrupts client protein interactions, leading to a dissociation of HSPA2 complexes and failure of oocyte recognition. Detailing the molecular nature of HSPA2 modifications will provide a strong platform for the targeted design of assisted reproduction therapies to alleviate the burden of male infertility.