Blood flow regulation is impaired in people with stroke. However, the time course of change in middle cerebral artery velocity (MCAv) following repeated stroke at rest and during exercise remains unknown. In this case study, we provide novel characterization of the dynamic kinetic MCAv response profile to moderate-intensity exercise before and after repeated ischemic MCA stroke. The initial stroke occurred in the left MCA. At 3 months poststroke, left MCAv amplitude (Amp) was ~50% lower than the right. At the 6-month follow-up visit, MCAv Amp declined in both MCA with the left MCAv Amp ~50% lower than the right MCAv Amp. Following a second right MCA stroke, we report further decline in Amp for the left MCA. At the 3- and 6-month visit following the second stroke, the left MCAv Amp declined further (~10%). The right MCAv Amp dramatically decreased by 81.3% when compared to the initial study visit. The MCAv kinetic analysis revealed a marked impairment in the cerebrovascular response to exercise following stroke. We discuss potential pathophysiological mechanisms contributing to poststroke cerebrovascular dysfunction and the need to test therapeutic interventions (such as exercise) that might attenuate cerebrovascular decline in people following stroke. © 2019 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.