In major depressive disorder (MDD), perfusion changes in cortico-limbic pathways are interpreted as altered neuronal activity, but they could also signify changes in neurovascular coupling due to altered capillary function. To examine capillary function in late-onset MDD, 22 patients and 22 age- and gender-matched controls underwent perfusion MRI. We measured normalized cerebral blood flow (nCBF), cerebral blood volume (nCBV), and relative transit-time heterogeneity (RTH). Resulting brain oxygenation was estimated in terms of oxygen tension and normalized metabolic rate of oxygen (nCMRO₂). Patients revealed signs of capillary dysfunction (elevated RTH) in the anterior prefrontal cortex and ventral anterior cingulate cortex bilaterally and in the left insulate cortex compared to controls, bilateral hypometabolism (parallel reductions of nCBV, nCBF, and CMRO₂) but preserved capillary function in the subthalamic nucleus and globus pallidus bilaterally, and hyperactivity with preserved capillary function (increased nCBF) in the cerebellum and brainstem. Our data support that perfusion changes in deep nuclei and cerebellum reflect abnormally low and high activity, respectively, in MDD patients, but suggest that microvascular pathology affects neurovascular coupling in ventral circuits. We speculate that microvascular pathology is important for our understanding of etiology of late-onset MDD as well as infererences about resulting brain activity changes.