The metabolic state of the awake rat’s cerebral cortex was evaluated by monitoring the intramitochondrial NADH redox state using the fiber optic-based surface fluorometry/reflectometry in real time. The blood supply to the brain was altered by occlusion of one or more blood vessels (arteries), for various intervals of time. Also, the evaluation of the energy state of the brain was tested by exposing the cerebral cortex to Cortical Spreading Depression (CSD) in normoxia and ischemia. The results show that in the rat even bilateral carotid arteries occlusion induced only partial ischemia due to the existence of the circle of Willis. In order to increase the level of ischemia in the rat, it was necessary to occlude three to four blood vessels providing blood to the brain. The metabolic response to CSD showed an oxidation cycle before occlusion and a few hours after the occlusion a reduction cycle of NADH was recorded. The effect of occlusion was reversible, and 7–8 days after the occlusion, the response to CSD was as before the occlusion. The effects of two types of anesthetics as well as partial ischemia on the response to complete ischemia (decapitation) were tested. The rate of NADH increase after decapitation was also significantly faster in the awake brain in comparison to the anesthetized one.