Bipolar Disorder (BD) is characterized by the occurrence of mania alternating with euthymia. The aim of the present study was to investigate the impact of BD on the autonomic nervous system, as indicated by heart rate variability (HRV). The study was registered in the Clinical Trials Registration (NCT01272518). Nineteen hospitalized, male patients (age: 34.0鈥?/-鈥?2.3 years) with type I BD were assessed during mania and at discharge on euthymia. HRV data were collected during 20- minutes in supine position at rest, on spontaneous breathing, using the Polar RS 800 CX frequencymeter. HRV measures included variables in time, frequency and non-linear domains. Psychiatric conditions were evaluated by the Mini International Neuropsychiatric Interview (MINI) and the Bech-Rafaelsen mania scale (BRMS). Time domain measures of RMSSD (Cohen\'s d鈥?鈥?.668) and pNN50 (Cohen\'s d鈥?鈥?.688) increased from first to second assessments. The high-frequency component (HFms2) also increased (Cohen\'s d鈥?鈥?.586), while the LF/HF ratio decreased (Cohen\'s d鈥?鈥?.785). Non-linear domain measures including the SD1 component (Cohen\'s d鈥?鈥?.668), and the SD1/SD2 ratio (Cohen\'s d鈥?鈥?.2934) extracted from the Poincare plot analysis increased from first to second assessment. The variables Lmean (Cohen\'s d鈥?鈥?.9627), Lmax (Cohen\'s d鈥?鈥?.2164), REC% (Cohen\'s d鈥?鈥?.0595) and EntShannon (Cohen\'s d鈥?鈥?.0607) were higher in mania. By contrast, ApEn (Cohen\'s d鈥?鈥?.995) and EntSample (Cohen\'s d鈥?鈥?.189) were less during mania, all reflecting ANS improvement. Findings are interpreted in the context of recently published models relating to neurovisceral integration across the continuum of time, and the implications for the future health and wellbeing of patients are considered.