INTRODUCTION Stable chronic obstructive pulmonary disease (COPD) patients often have lower airway bacterial colonization (ABC) which may modulate exacerbation frequency. Data regarding the association between ABC and post-procedural COPD exacerbations following bronchoscopic lung volume reduction (BLVR) are scant. OBJECTIVES Our aim was to explore the correlation among ABC, serum C-reactive protein (CRP) level and the risk of COPD exacerbation within a month following BLVR. METHODS Pre-procedure bronchoalveolar lavage (BAL) quantitative bacterial cultures and serum levels of CRP were evaluated in severe COPD patients (N = 70, mean FEV1 = 34.6%) before BLVR by polymeric lung sealant. RESULTS Colonization with potential pathogenic microorganism (PPM) was observed in 40 (57.1%) patients. Out of 28 patients (40%) who had COPD exacerbation within 30 days of BLVR, 23 (82.1%) had PPM in BAL culture compared with only 14 (33.3%) out of 42 patients who had uneventful procedure (P = 0.0027). Serum CRP level was significantly higher in patients with exacerbation compared with those with no exacerbation (mean 47.8 ± 66.0 mg/L vs 13.05 ± 27.7 mg/L, respectively, P = 0.0063). The combination of CRP level above 3.12 mg/L and PPM growth in BAL was observed in 89.2% of patients with exacerbation compared with only 52.3% of patients without exacerbation (P = 0.0031). CONCLUSIONS ABC is common in severe COPD patients undergoing BLVR, and along with elevated CRP level both are associated with high risk of immediate post-procedural COPD exacerbation. These patients should be identified, carefully observed and possibly benefit from prophylactic microbiologically directed antibiotic treatment.