The objective of this investigation was to verify the hypothesis that the presence of lower airway bacterial colonization (LABC) can be a stimulating factor of airway inflammation, more frequent exacerbation, and impact on pulmonary function, independent of current tobacco smoking in the stable phase of chronic obstructive pulmonary disease (COPD). A total of 46 ex-smokers with moderate to severe COPD, 19 healthy non-smokers, and 17 ex-smokers without COPD were included in this study. Their sputum specimens were collected at the first baseline visit and at the second visit after a follow-up of one year. The samples were analyzed for bacterial growth by culture, and the levels of interleukin (IL)-6, IL-8, and tumor necrosis factor alpha (TNF-α) were measured by enzyme-linked immunosorbent assay (ELISA). The frequencies of exacerbations and pulmonary function were compared at visit 2. At visit 1, 37.0% (17/46) were found to have LABC with bacterial loads ≥10⁶ CFU/ml in their sputum specimens. Haemophilus influenzae was the predominant pathogenic organism isolated. IL-8, IL-6, and TNF-α in these patients' sputum were significantly higher than those without LABC (p < 0.05). It was the presence of LABC that contributed to the significantly elevated IL-8 and IL-6 at the 1-year period (p < 0.05). LABC was also associated with significantly increased frequencies of exacerbations and declined forced expiratory volume in 1 s (FEV₁) (p < 0.05). LABC was documented in a subpopulation of stable COPD patients; it may be responsible for the deterioration of pulmonary function of COPD patients by promoting airway inflammation and/or increased frequency of exacerbations independently of tobacco smoking.