Chronic obstructive pulmonary disease (COPD) is a common respiratory disease with episodes of exacerbation. Variable factors including infectious pathogen can predispose for this exacerbation. The aim of this study is to evaluate the role of intestinal protozoa in COPD exacerbation. A total of 56 patients with COPD were included in this study. Patients were categorized into two groups based on the frequency of exacerbation during the last 6 months: those with ≤1 exacerbation (32 patients) and those with ≥2 exacerbations (24 patients). Stool specimens from each patient were collected two times (one week interval) examined for intestinal parasite. In univariate analysis, rural residence and parasitic infection were more common among patients with frequent exacerbation (45.83% and 33.33%, respectively) than patients with non-frequent exacerbation (18.75% and 9.38%, respectively) with significant differences. However, in multivariate analysis, only body mass index >25 kg/m2 (OR=4.59, 95%CI=1.18-17.86, P=0.028) and parasitic infection (OR=5.51, 95%CI=1.01-30.18, P=0.049) were independently associated with COPD exacerbation. These data indicate a significant association between frequent COPD exacerbation and infection with some intestinal protozoa. However, the cause-effect relationship is debatable.