A method and system are provided which are useful for the non-invasive determination and monitoring of cerebral tissue oxygenation. The method comprises the steps of generating at least first and second jugular venous output signals against time based on the reflection of at least first and second wavelengths of light, respectively, from an external tissue site on the patient in the proximity of the internal jugular vein; obtaining corresponding first and second cardiac arterial output signals for the first and second wavelengths of light, respectively, from the patient, and separating the first and second cardiac arterial output signals from the first and second jugular venous output signals, respectively, to generate first and second cerebral venous output signals; and determining cerebral tissue oxygenation based on the first and second cerebral venous output signals. A system useful to monitor cerebral tissue oxygenation may comprise a first module for optically generating at least first and second jugular venous output signals against time at at least first and second wavelengths of light, respectively, from the patient; a second module for generating first and second cardiac arterial output signals at the first and second wavelengths of light, respectively, from the patient; and a signal processing means adapted to separate the first and second cardiac arterial output signals from the first and second jugular venous output signals, respectively, to yield first and second cerebral venous output signals, for the determination of cerebral tissue oxygenation.