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Cigarette smoke contains harmful chemicals with deleterious health effects leading to oxidative stress and neuronal damage. This study investigated the levels of serum cotinine (COT), thiocyanate (thioc), uric acid (UA), neuron specific enolase (NSE), and the association between these variables in cigarette smokers. This cross sectional study enrolled 60 cigarette smokers and 45 non-smokers as participants. Serum thiocyanate and UA were estimated by colorimetric methods. Serum cotinine and NSE were determined by ELISA methods. Height and weight were measured and BMI computed. Data were analyzed using Student’s t-test, ANOVA, and Pearson’s correlation at P<0.05. Serum cotinine, thioc and NSE concentrations were significantly higher while BMI and UA levels were significantly lower (P<0.05) in smokers than in the controls. Age was not significantly different between the two groups (P>0.05). Age, COT, UA, thioc and NSE vary significantly (P<0.05) between the light, moderate and heavy cigarette smokers. From the least significant difference post hoc analyses, the mean age and UA level of light smoker were significantly higher (P<0.05) compared with the moderate smokers, while COT level of moderate smokers was significantly higher (P<0.05) compared with light smokers. Neuron specific enolase level of moderate cigarette smokers was higher (P>0.05) compared with the light smokers. The mean age of light smokers was significantly higher (P<0.05) compared with the heavy smokers, while the COT, thioc and NSE levels of light smokers were significantly lower (P<0.05) compared with the heavy smokers. Serum UA, thioc and NSE levels of moderate smokers were significantly lower (P<0.05), than those of the heavy smokers. Significant negative correlations were observed between age and COT (r = -0.554, P<0.001), age and thioc (r = -0.421, P= 0.001), age and NSE (r = -0.346, P=0.001), age against smoking pack years (r = -0.623, P<0.001) respectively. Significant positive correlations were observed between serum thioc and NSE (r = 0.324, P=0.012), COT against smoking pack years (r = 0.399, P=0.002), and NSE against smoking pack years (r = 0.311, P=0.015), correspondingly. This study has shown that high levels of cotinine and thiocyanate are associated with increased levels of neuron specific enolase, smoking pack years and decreased uric acid in smokers.