Abstract Purpose The purpose of the study was to investigate longitudinally over time heart rate (HR) and blood pressure variability and baroreflex sensitivity in acute brain injury patients and relate them with the severity of neurologic dysfunction and outcome. Methods Data from 20 brain injured patients due to multiple causes and treated in the intensive care unit were used, with HR and blood pressure recorded from monitors and analyzed on a daily basis. We performed power spectral analysis estimating low frequencies (LF: 0.04-0.15 Hz), high frequencies (HF: 0.15-0.4 Hz), and their ratio and calculated the approximate entropy, which assesses periodicity within a signal and transfer function (TF), that estimates baroreflex sensitivity. Heart rate variance was considered as a measure of HR variability. Results Nonsurvivors (brain dead) had lower approximate entropy (0.65 ± 0.24 vs 0.84 ± 0.26, P < .05) and lower variance mean values (0.48 ± 0.54 vs 1.29 ± 0.42 ms2 /Hz, P < .01), lower LF and HF minimum values (0.31 ± 0.88 vs 1.11 ± 0.46, P < .01; and 0.27 ± 0.42 vs 0.86 ± 0.30, P < .01, respectively), lower LF/HF (0.22 ± 0.29 vs 0.62 ± 0.28, P < .01), and lower TF mean values (0.43 ± 0.29 vs 1.11 ± 0.74, P < .05) during their whole stay in the intensive care unit in relation with survivors. The mean variance ( P < .05), mean TF ( P < .05), and mean LF/HF ( P < .05) were significantly successful in separating survivors from nonsurvivors. Conclusions We conclude that in acute brain injury patients, low variability, low baroreflex sensitivity, and sustained decrease in LF/HF of HR signals are linked with a high mortality rate.