The goal of this work is to study the cerebral autoregulation, brain gas exchange, and their interaction by means of a mathematical model. We have previously developed a model of the human cardiopulmonary (CP) system, which includes the whole body circulatory system, lung and peripheral tissue gas exchange, and the central nervous system control of arterial pressure and ventilation. In the current study, we add a more detailed description of cerebral circulation, cerebrospinal fluid (CSF) dynamics, brain gas exchange and cerebral blood flow (CBF) autoregulation. Two CBF regulatory mechanisms are included: autoregulation and CO₂ reactivity. Central chemoreceptor control of ventilation is also included. We first establish nominal operating conditions for the cerebral model in an open-loop configuration using data generated by the CP model as inputs. The cerebral model is then integrated into the larger CP model to form a new integrated CP model, which is subsequently used to study cerebral hemodynamic and gas exchange responses to test protocols commonly used in the assessment of CBF autoregulation (e.g., carotid artery compression and the thigh cuff deflation test). The model can closely mimic the experimental findings and provide biophysically based insights into the dynamics of cerebral autoregulation and brain tissue gas-exchange, as well as the mechanisms of their interaction during the simulation of test protocols which are aimed at assessing the degree of autoregulation. With further refinement, our CP model may be used on measured data associated with the clinical evaluation of the cerebral autoregulation and brain oxygenation in patients.