Artificial ventilation with positive end-expiratory pressure (PEEP) is commonly applied for brain damaged patients. However, the effect of the ventilation on brain function, including cardiovascular autonomic nervous system (CANS) activity, is not well elucidated. In order to investigate the effect of 5cmH_2O PEEP on CANS activity in brain damaged rabbits under general anesthesia, we produced acute brain damage by intracranial balloon inflation. Measurements were made before (control) and after application of PEEP, and after inflation with incremental volume of the balloon. Power spectral analyses of heart rate variability (HRV) and systolic arterial pressure variability (SAPV) were used for the assessment of CANS activity. Spectral powers in the low-frequency range of 0.04 to 0.40 Hz (LF) and high-frequency range of 0.75 to 1.40 Hz (HF) were computed, and their ratio LF/HF was assessed as the neural balance of CANS. The animals in group P were ventilated with 5cm H_2O PEEP, while those in group Z were ventilated with zero end-expiratory pressure. Colored microsphere counting was used for the assessment of brain circulation. In the results, PEEP had no effect on HRV and SAPV parameters before induction of brain damage. After inflation with incremental volume of the balloon, log (HF) and log (LF) in group P were lower than in group Z in HRV analysis, and log (LF) in group P was lower than in group Z in SAPV analysis. Microsphere counting revealed that brain blood flow was reduced during the progression of brain damage and showed a significant difference after application of PEEP between the groups. We concluded that 5cmH_2O PEEP depressed CANS activity during the progression of brain damage in rabbits and that this was partly due to aggravated brain function induced by PEEP.