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Key Points Male infertility is a complex lifestyle-related disorder Oxidative stress has adverse effects on the structural and functional integrity of sperm and is a major cause of defective sperm function and male infertility Oxidative stress causes damage to both mitochondrial and nuclear DNA and also affects the sperm epigenome, resulting in infertility, recurrent pregnancy loss, poor pregnancy outcomes and an increased disease burden in the offspring Spermatozoa are most vulnerable to oxidative stress and oxidative DNA damage (ODD) as these cells have limited antioxidant defence mechanisms and a limited capacity for detection and repair of DNA damage A number of intrinsic and extrinsic factors can regulate oxidative stress, and these must be maintained at moderate levels for optimal sperm function and the maintenance of cellular homeostasis and redox-sensitive signal-transduction pathways Simple lifestyle modifications and interventions can substantially reduce levels of testicular inflammation, oxidative stress and ODD and improve the quality of life of infertile couples Abstract DNA damage, largely owing to oxidative stress, is a leading cause of defective sperm function