BACKGROUND: Propofol causes significant cardiovascular depression and a slowing of neurophysiological activity. However, literature on its effect on the heart rate remains mixed, and it is not known whether cortical slow waves are related to cardiac activity in propofol anesthesia. METHODS: We performed a secondary analysis of ECG and EEG data collected as part of a previously published study where N=16 healthy volunteers underwent a slow infusion of propofol up to an estimated effect-site concentration of 4 µg/ml. Heart rate, heart rate variability, and individual slow EEG waves were extracted for each subject. Timing between slow-wave start and the preceding R-wave was tested against a uniform random surrogate. Heart rate data were further examined as a post hoc analysis in N=96 ASA-2/3 older clinical population collected as part of the AlphaMax trial. RESULTS: The slow propofol infusion increased the heart rate in a dose-dependent manner (increase of +4.2 ± 1.5 bpm/(μg ml-1), P<0.001). The effect was smaller but still significant in the older clinical population. In healthy volunteers, propofol decreased the ECG R-wave amplitude (decrease of -83 [-245, -28] μV, P<0.001). Heart rate variability showed a loss of high-frequency parasympathetic activity. Individual cortical slow waves were coupled to the heartbeat. Heartbeat incidence peaked about 450ms before slow-wave onset and mean slow-wave frequency correlated with mean heart rate. CONCLUSIONS: We observed a robust increase in heart rate with increasing propofol concentrations in healthy volunteers and patients. This was likely due to decreased parasympathetic cardio-inhibition. Similar to non-rapid eye movement sleep, cortical slow waves are coupled to the cardiac rhythm, perhaps due to a common brainstem generator.