Background: Nicotine abuse through cigarette smoking is a major public health problem. Nicotine induces a production of free radicals and consequently oxidative stress. Selenium is a micronutrient and element present in trace amounts in living organism. Vitamin-C (Ascorbic acid) is a water-soluble antioxidant which has a multifunction. It helps to strengthen the immune system and it prevents some diseases, play important role in the brain, nervous system, and immune system. Aim of work: The current study aimed to investigate the effects the toxic effects of nicotine and to evaluate the role of Selenium and Vitamin C in protecting the hemo-toxicity, hormonal toxicity, reproductive system toxicity and oxidative damage induced by nicotine in experimental animals represented in adult male albino rat. Material and methods: This work was performed on 66 adult male albino rats weighing between 100-120 mg. The animals were divided into 7 groups, each containing 6 animals. All groups were treated daily, for 4 weeks. The Study Design was distributed as: Negative control group, Positive control group, Nicotine group, Selenium group, Vitamin C group, Nicotine with Selenium group and finally Nicotine with Vitamin C group. Results: Our results displayed significantly that oral administration of Nicotine induced toxic effects, hormonal changes and hematological damage in the testes and these adverse effects may be attributed to induction of oxidative stress. Administration of Selenium and Vitamin C with Nicotine, protected against Nicotine damaging effect.