During general anesthesia positive pressure mechanical ventilation (MV) profoundly affects intrathoracic pressure and venous return, thus soliciting cardiopulmonary reflexes and modifying stroke volume. As a consequence heart period, approximated as the temporal distance between two consecutive R peaks on the ECG (RR), and systolic arterial pressure (SAP) variability series are usually highly correlated at the MV frequency (MVF) and this significant correlation is commonly taken as an indication of an active baroreflex. In this study the involvement of baroreflex was tested according to a time-domain linear Granger causality approach accounting explicitly for MV in two experimental protocols. In the first protocol volatile (VA) or intravenous (IA) anesthetic was administered in humans during pressure controlled MV (PCMV). In the second protocol IA was administered in pigs during PCMV or pressure support MV (PSMV). Causality analysis was contrasted with RR-SAP squared coherence. Significant coherence values at MVF were always found in both protocols. On the contrary, a significant causal link from SAP to RR was less frequently found in humans independently of the anesthesiological strategy and in animals during PCMV. PSMV was superior to PCMV in animals because it was able to better preserve a link from SAP to RR. During general anesthesia the involvement of baroreflex in governing RR-SAP variability interactions is largely overestimated by RR-SAP squared coherence and causality analysis can be exploited to rank anesthesiological strategies and MV modes according to the ability of preserving a working baroreflex.