Heart rate and blood pressure variations during spontaneous ventilation are related to the negative airway pressure during inspiration. Inspiratory airway pressure is positive during mechanical ventilation, suggesting that reversal of the normal baroreflex-mediated pattern of variability may occur. We investigated heart rate and blood pressure variability and baroreflex sensitivity in 17 mechanically ventilated patients. ECG (RR intervals), invasive systolic blood pressure (SBP), and respiratory flow signals were recorded. High Frequency (HF) amplitude of RR and SBP time series and HF phase differences between RR, SBP and ventilatory signals were continuously computed by Complex DeModulation (CDM). Cross spectral analysis was used to assess the coherence and the gain functions between RR and SBP, yielding baroreflex sensitivity indices. The HF phase difference between SBP and ventilatory signals was nearly constant in all patients, with inversion of SBP variability during the ventilator cycle compared to cycling with negative inspiratory pressure to replicate spontaneous breathing. In 12 patients (group 1), the phase difference between RR and ventilatory signals changed over time and the HF-RR amplitude varied. In the remaining 5 patients (group 2), RR-ventilatory signal phase and HF-RR amplitude showed little change; however, only 1 of these patients exhibited a RR-ventilatory signal phase difference mimicking the normal pattern of respiratory sinus arrhythmia. Spectral coherence between RR and SBP was lower in the group with phase-difference changes. Positive pressure ventilation exerts mainly a mechanical effect on SBP, whereas its influence on HR variability seems more complex, suggesting a role for neural influences.