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Oxidative stress is induced by tobacco smoking and is also associated with exposure to air pollution, which are two of the most important risk factors for chronic obstructive pulmonary disease (COPD). The aim of this study was to correlate tobacco use and exposure to air pollution with oxidative stress markers useful in clinical practice in patients with COPD. A total of 102 patients were included and the levels of polycyclic aromatic hydrocarbons (PAHs), malondialdehyde, uric acid and number of packs-years (PY) were determined. Also, six different ratios were used to assess the source of exposure. The results obtained in this study show an admission of pollutants according to smoking status (former smokers/smoker/non-smokers) quantified in average total concentrations for the group of patients with COPD of 4.12 ng/mL, 6.76 ng/mL, 6.04 ng/mL. The six ratios used show that in COPD, the content of PAHs in the blood could be a result of diesel emissions and fuel combustion. Uric acid levels were lower in the smoker group of COPD patients (mean = 5.21 mg/dL), which indicates that oxidative stress is intensified with each cigarette smoked. Additionally, high concentrations of malondialdehyde were quantified for smoking patients diagnosed with COPD (mean = 2.72 µmol/L) compared to former smokers (mean = 2.43 µmol/L) and non-smoking (mean = 2.32 µmol/L) patients, which is another indicator of the implication of smoking in oxidative stress in COPD patients.