Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the commonest inherited stroke disorder. We report a novel presentation of multiple internal border zone infarcts in a patient with COVID-19 and CADASIL. The clinical significance of this case is to highlight the risk of COVID-19 exacerbating CADASIL. Possible pathophysiological mechanisms are discussed, which may be extrapolated to patients with cerebral small vessel disease and non-CADASIL strokes.