BACKGROUND The cigarette compounds are associated with the increase in the incidence of oral cancer and precancerous lesions. Salivary antioxidant system plays an important role in anti-carcinogenic capacity of saliva. Cotinine, a nicotine metabolite, has a longer half-life in comparison with nicotine and is a suitable marker for exposure to cigarette smoke. This study aims to measure total antioxidant capacity (TAC) and cotinine level in saliva of smokers and non-smokers and compare salivary cotinine level and TAC in each group. METHODS In this cross-sectional study, 32 smokers and 34 non-smokers were recruited by consecutive sampling from Department of Oral Medicine, School of Dentistry, Mashhad University of Medical Sciences, Mashhad, Iran. Salivary cotinine and TAC concentrations were determined using the enzyme-linked immunosorbent assay (ELISA) technique. For data analysis, correlation tests of Spearman, Mann-Whitney U, and independent samples t-test were used. RESULTS A significant difference was observed between the two groups in the mean cotinine level and in the mean TAC (P = 0.015, P = 0.027, respectively). TAC showed a weak negative correlation with the cotinine level, but the difference was not significant (P = 0.651). CONCLUSIONS Antioxidants are of great importance to smokers because antioxidants are able to scavenge free radicals found in cigarette smoke. According to the results of present study, the salivary TAC in smokers was lower than that of non-smokers, and the salivary cotinine level in smokers was higher than non-smokers. Therefore, smoking endangers the oral cavity health by reducing the salivary TAC. Further studies with a higher sample size and other factors affecting the salivary TAC are needed for definitive comment.