This study was aimed at determining the extent of sperm nuclear DNA damage in patients with isolated teratozoospermia and examining its relationship with oxidative stress.Semen samples from 60 patients with isolated teratozoospermia and 30 normozoospermic donors were examined. DNA damage was evaluated by the COMET assay. Seminal antioxidant activities (Superoxide dismutase; Glutathione peroxidase; Catalase), iron and malondialdehyde concentrations were measured spectrophotometrically.Sperm DNA damage; malondialdehyde and iron levels were more elevated in studied groups than controls. Nevertheless, the antioxidant enzyme activity obtained was significantly lower in the group of patients with teratozoospermia compared to the controls. Sperm DNA damage was positively correlated to malondialdehyde and seminal iron level while reduced seminal antioxidant status was negatively associated with sperm DNA breaks. Interestingly, we noted that sperm DNA damage; lipid peroxidation, iron level, and impaired antioxidant status were negatively correlated to normal sperm morphology.These findings may explain the complex biological relationship between teratozoospermia, oxidative stress, and DNA damage. In fact, an impaired seminal antioxidant status and an increased seminal level of both lipid peroxidation and iron can affect sperm nuclear integrity resulting in DNA breaks and can be associated with poor sperm morphology.