Reduced heart rate variability (HRV) is a predictor of poor outcome in several pathologies and in general population. Whether HRV is altered during normal daily activities or influenced by anticholinergic and beta-adrenergic medications in chronic obstructive pulmonary disease (COPD) remains unknown. Forty-one clinically stable COPD patients and 19 healthy controls matched for age, sex and smoking history underwent a 24-hour ambulatory ECG recording during normal daily activities. HRV was assessed by standardized temporal and spectral analysis. COPD patients showed a reduced HRV (LF/HF ratio) compared with healthy controls (median [interquartile range]) during daytime (2.6 [1.5-3.8] vs. 3.5 [2.9-5.6]), nighttime (1.8 [1.1-4.3] vs. 4.2 [2.7-6.9]) as well as during the entire 24-hour (1.9 [1.5-3.4] vs. 3.9 [3.2-5.6]) recordings (all P < 0.005). There was no significant difference between the two groups in the time domain and in the low frequency or high frequency domain for the 24-hour period analysis. In COPD patients, the 24-hour LF/HF ratio positively correlated with forced expiratory volume in 1 second (FEV(1)) (r = 0.342, P = 0.028) and negatively correlated with age (r = -0.317, P = 0.044). In multiple regression analysis, LF/HF ratio was associated with FEV(1) (P = 0.05) but not with age (P = 0.08). There was no difference of HRV between patients using or not anticholinergic or beta-agonist medications. These results demonstrate that COPD patients have a reduced sympatho-vagal balance compared with healthy subjects. HRV correlates with disease severity and does not seem to be influenced by anticholinergic or adrenergic medications.