Background: Whether autonomic dysfunction contributes to tachycardia in cystic fibrosis (CF) is unknown. Methods: Heart rate variability (HRV) was assessed to determine high frequency power and the low/high frequency power ratio (HF, LF/HF) as markers of vagal and sympathovagal balance, respectively, under spontaneous and controlled breathing (15 breaths per minute (bpm)) conditions in 17 CF and 17 healthy control subjects. Results: Under spontaneously breathing conditions, the CF group was tachycardic (75.4 11.2 vs 60.2 9.0 br/min P < 0.001) and tachypnoeic (22.6 5.8 vs 13.6 4.1 br/min, P = 0.001) compared with controls. No significant difference in HRV was observed between groups during spontaneous or controlled breathing. Coexistent diabetes mellitus and b2 agonist use were not associated with altered autonomic control. During controlled breathing, the CF group showed a negative correlation between forced expiratory volume in 1 s (FEV1) % predicted and HF power (P = 0.013, r = -0.59) and a positive correlation between FEV1 % predicted and LF/HF ratio (P = 0.002, r = 0.69) suggesting an exaggerated normal vagal response. Conclusion: CF patients have normal autonomic function.