Both cigarette smoking and strenuous physical work are associated with increased oxidative stress, which is implicated in the pathogenesis of cardiovascular disease. No study to date has measured oxidative stress in response to graded exercise in cigarette smokers. We compared oxidative stress biomarkers before and after strenuous exercise (Bruce treadmill protocol) in 14 cigarette smokers and 15 nonsmokers of similar age (24±6 years) and fitness status. Plasma protein carbonyls (PC), malondialdehyde (MDA), and 8-hydroxydeoxyguanosine (8-OHdG) were measured pre- and postexercise. Smoking status (p<.01) and time (p<.01) effects were noted for PC with values higher for smokers than nonsmokers and increasing from pre- to postexercise (52% vs. 25%, respectively). The smoking statustime interaction for PC approached statistical significance (p = .07). The change in PC from pre- to postexercise was positively correlated with the number of cigarettes smoked per day (r = .5782, p = .03). A smoking statustime interaction was noted for MDA (p<.01), with values increasing 37% from pre- (0.6140±0.0708 µmol/L) to postexercise (0.8440±0.0687 µmol/L) for smokers and remaining relatively unchanged for nonsmokers (from 0.7664±0.0901 to 0.7419±0.0776 µmol/L). 8-OHdG was unaffected by smoking status (p = .43) or exercise (p = .40). These findings indicate that young cigarette smokers experience an exaggerated oxidative stress response to strenuous physical work, compared with nonsmokers of similar age. These results highlight yet another detrimental impact of cigarette smoking on human health. Future investigations should focus on older, more established smokers.