Background: Acne vulgaris is a multifactorial skin disorder of unknown etiology. Free radical-mediated reactions have been implicated but their role in eliciting this response and contributing to disease progress remains unexplored. Vitiligo is an idiopathic, acquired, circumscribed, hypomelanotic skin disorder, characterized by milky white patches of different sizes and shapes. It is due to the destruction of melanocytes resulting in the absence of pigment production of the skin and mucosal surfaces. Oxidative stress has been implicated in pathophysiology of vitiligo which is considered one of the major hypotheses in the pathogenesis of vitiligo. Objective: This work was done to evaluate the extent of oxidative stress and DNA damage in patients with acne vulgaris in comparison to patients with vitiligo, a disease with a well-known and documented role of oxidative stress in its pathogenesis. The study also hoping the possibilities of adding antioxidants therapy as a new adjuvant modality in patients with acne vulgaris, the same way they were recently added to routine vitiligo therapy. Patients and Methods: Serum from 15 patients of acne vulgaris, 15 patients of vitiligo and 15 age and sex-matched controls were evaluated for serum levels of superoxide dismutase (SOD), malondialdehyde (MDA) and DNA damage. Results: In both acne vulgaris and vitiligo patients, serum level of MDA and percentage of DNA damage were statistically significantly higher compared to control while serum level of SOD was statistically significantly lower than control. Comparing acne vulgaris with vitiligo patients revealed that serum level of MDA and percentage of DNA damage in vitiligo were statistically significantly higher compared to acne vulgaris and serum level of SOD in vitiligo was statistically significantly lower compared to acne vulgaris. Comparing between mild and moderate acne vulgaris patients and vitiligo patients regarding the serum level of MDA and percentage of DNA damage, vitiligo was found to be statistically significantly higher, however comparing between severe acne vulgaris patients and vitiligo patients, no statistically significant difference was found between them. Serum level of SOD was statistically significantly lower in vitiligo patients compared to acne vulgaris patients irrespective to disease severity. Conclusion : DNA damage appears to be a more sensitive and accurate marker of oxidative stress. Hence, it should be used as an indicative marker of oxidative stress, besides measuring MDA and SOD serum levels. Oxidative stress in severe cases of acne vulgaris was found to be as equal as in vitiligo cases, a finding that suggests the addition of antioxidants to the treatment regimen of acne vulgaris the same way they were added to the treatment regimen of vitiligo cases few years ago. The exact extent of oxidative stress and the possible role of antioxidants in mild and moderate cases of acne will probably need further investigation by future studies.