Sulfur mustard (SM) is a cytotoxic and chemical agent that targets different tissues such as reproductive system. SM causes a wide variety of pathological effects on reproductive system such as disturbance in reproductive hormones, testis atrophy, spermatogenesis deficiency, low quality of sperm and fertility problem. However, molecular and cellular mechanisms of its adverse effects are still not well known. General events such as tissue damage, inflammation, DNA alkylation, cell membrane defects, apoptosis and cell death are observed frequently in SM-exposed subjects. Oxidative stress (OS) and antioxidants depletion induced by SM seem to be one of the main factors that lead to low sperm quality and male infertility among exposed patients. It is believed that SM can trigger several molecular and cellular pathways linked to OS and inflammation in reproductive system that can cause impaired spermatogenesis, sperm apoptosis and poor sperm quality as well as loss of tissue structure and function. Identification of these signaling pathways and molecules gives us valuable information regarding the mechanisms of SM effect on reproductive dysfunction and the way for developing a better clinical treatment. Therefore, in this review we aimed to discuss the proposed cellular and molecular mechanisms of SM effect on reproductive system, the significance of oxidative stress and the mechanisms by which SM induces OS and antioxidants depletion in SM exposed men.