Objective: The new theory of holistic integrative physiology and medicine, which describes the integrative regulation of respiratory, circulatory and metabolic systems in human body, generates the hypothesis of that breath is the origin of variability of circulatory parameters. We investigated the origin of heart rate variability by analyzing relationship between the breath and heart rate variability (HRV) during sleep. Methods: This retrospective study analyzed 8 normal subjects (NS) and 10 patients of chronic diseases without sleep apnea (CDs-no-SA). After signed the informed consent form, they performed cardiopulmonary exercise testing (CPET) in Fuwai Hospital and monitored polysomnography (PSG) and electrocardiogram (ECG) during sleep since 2014. We dominantly analyzed the correlation between the respiratory cycle during sleep and the heart rate variability cycle of the ECG R-R interval. The HRV cycle included the HR increase from the lowest to the highest and decrease from the highest to the lowest point. The number of HRV (HRV-n), average HRV time and other parameters were calculated. The breath cycle included complete inhalation and subsequent exhalation. The number of breath (B-n), average breath time and other breath parameters were analyzed and calculated. We analyzed each person's relationship between breath and HRV; and the similarities and differences between the NS and CDs-no-SA groups. Independent sample t test was used for statistical analysis, with P<0.05. Results: CPET core parameter such as Peak VO2 (83.8±8.9)% in NS were significantly higher than that (70.1±14.9)% in patients of chronic diseases without sleep apnea (P<0.05), but there was no difference between their AHI (1.7±1.3) in NS and AHI (2.9±1.2) in CDs-no-SA (P>0.05). The B-n and the HRV-n (6581.63±1411.90 vs 6638.38±1459.46), the average B time and the average HRV time (4.19±0.57)s vs (4.16±0.62)s in NS were similar without significant difference (P>0.05). The comparison of the numbers in CDs-no-SA were the number (7354.50±1443.50 vs 7291.20±1399.31) and the average times ((4.20±0.69)s vs (4.23±0.68)s) of B and HRV were similar without significant difference (P>0.05). The ratios of B-n/HRV-n in NS and CDs-no-SA were (0.993±0.027 vs 1.008±0.024) and both were close to 1 and similar without significant difference (P>0.05). The average magnitude of HRV in NS ((5.74±3.21) bpm) was significantly higher than that in CDs-no-SA ((2.88±1.44) bpm) (P<0.05). Conclusion: Regardless of the functional status of NS and CDs-no-SA, there is a similar consistency between B and HRV. The origin of initiating factors of HRV is the respiration.