IMPORTANCE Neurobiological models of obsessive-compulsive disorder (OCD) predict hyperactivity in brain circuits involving the orbitofrontal cortex and the basal ganglia, but it is unclear whether these areas are also characterized by altered brain network properties. OBJECTIVES To determine regions of abnormal degree connectivity in patients with OCD and to investigate whether connectivity measures are affected by antidepressant medication in OCD. DESIGN Case-control cross-sectional study using resting-state functional magnetic resonance imaging and a data-driven, model-free method to test for alterations in the degree of whole-brain, distant, and local connectivity in unmedicated patients with OCD compared with healthy controls. SETTING Outpatient clinic for OCD. PARTICIPANTS Twenty-three patients with OCD (12 women, 11 men) receiving no medication, 23 patients with OCD (14 women, 9 men) treated with antidepressant medication, and 2 equally sized control samples matched for age, sex, handedness, educational level, and IQ. MAIN OUTCOME MEASURES Statistical parametric maps testing the degree of distant and local functional connectivity of each voxel (hub analysis at voxel level) and OCD symptom severity. RESULTS Unmedicated patients with OCD showed greater distant connectivity in the orbitofrontal cortex and subthalamic nucleus and greater local connectivity in the orbitofrontal cortex and the putamen. Furthermore, distant connectivity of the orbitofrontal cortex and the putamen positively correlated with global OCD symptom severity. Medicated patients with OCD showed reduced local connectivity of the ventral striatum compared with the unmedicated patients. CONCLUSIONS AND RELEVANCE Consistent with neurobiological models of OCD, the orbitofrontal cortex and the basal ganglia are hyperconnected in unmedicated patients. The finding of distant connectivity alterations of the orbitofrontal cortex and the basal ganglia represents initial evidence of greater connections with distant cortical areas outside of corticostriatal circuitry. Furthermore, these data suggest that antidepressant medication may reduce connectivity within corticobasal ganglia-thalamo-cortical circuits in OCD.