We exploited two-photon microscopy and Doppler optical coherence tomography to examine the cerebral blood flow and tissue pO2 response to forced treadmill exercise in awake mice. To our knowledge, this is the first study performing both direct measure of brain tissue pO2 during acute forced exercise and underlying microvascular response at capillary and non-capillary levels. We observed that cerebral perfusion and oxygenation are enhanced during running at 5 m/min compared to rest. At faster running speeds (10 and 15 m/min), decreasing trends in arteriolar and capillary flow speed were observed, which could be due to cerebral autoregulation and constriction of arterioles in response to blood pressure increase. However, tissue pO2 was maintained, likely due to an increase in RBC linear density. Higher cerebral oxygenation at exercise levels 5-15 m/min suggests beneficial effects of exercise in situations where oxygen delivery to the brain is compromised, such as in aging, atherosclerosis and Alzheimer Disease.