During mechanical ventilation, large inter-patient and intra-patient variations of the phase of respiratory sinus arrhythmia (RSA) were described. To determine whether these variations were neurally mediated, we compared the RSA phase between: (1) 12 control subjects, (2) 23 mechanically ventilated patients without brain injury (MV group) and (3) 12 brain dead, mechanically ventilated patients, whose central nervous functions were abolished (BD group). ECG and ventilatory flow were recorded during 15 min and the RSA phase was then continuously computed by complex demodulation. Control group exhibited RSA phases between 180° and 250° whereas an opposite pattern, between 0° and 90°, was observed in the BD group. For the two groups, the phase was stable over time. In the MV group, the RSA phases were distributed between 0° and 260°, with a greater variability over time than the other groups. Therefore, during mechanical ventilation, brainstem centers may induce large variations of the RSA phase, not synchronous with the mechanical effect of ventilation.