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It is unknown whether changes in cerebral small vessel disease (SVD) are limited to the brain or part of a generalized vascular disorder.We examined the sublingual microcirculation of 10 healthy controls, 10 patients with large vessel disease, and 8 with SVD, with side-stream dark field imaging. We analyzed 146 video fragments masked to the origin of the videos. Imaging software measured the functional capillary density per tissue surface unit. We scored the percentage of blood vessels with abnormal flow (abnormal flow index) and the presence of extravascular erythrocyte material as presumed evidence of past microbleeds or obliterated vessels.Functional capillary density differed between the 3 groups (SVD, large vessel disease, and controls; means, 14.8, 17.0, and 16.1 mm/mm2; P=0.01). Abnormal flow was more frequent in SVD patients compared with large vessel disease patients and controls (medians, 10.5%, 6.1%, 5.5%; P=0.04). Extravascular erythrocyte material was almost exclusively present in patients with SVD (P=0.004).We found evidence of pathological changes in the sublingual microcirculation in patients with cerebral small vessel disease, which suggests that cerebral SVD is part of a generalized vascular disorder.