Clinical and neuroimaging data support the idea that schizo-obsessive comorbidity (SOC), similar to obsessive-compulsive disorder (OCD) and schizophrenia (SCZ), may be a distinct brain disorder. In this study, we examined the strength of resting-state functional connectivity (rsFC) between 19 subregions of the default mode network (DMN) and whole brain voxels in 22 patients with SOC features, 20 patients with SCZ alone, 22 patients with OCD, and 22 healthy controls (HC). The main results demonstrated that patients with SOC exhibited the highest rsFC strength within subregions of the DMN and the lowest rsFC strength between the DMN and subregions of the salience network (SN) compared with the other 3 groups. In addition, compared with HCs, all 3 patient groups exhibited increased rsFC between subregions of the DMN and the executive control network (ECN). The SOC and SCZ group both exhibited increased rsFC between subregions of the DMN and the middle temporal gyrus, but the OCD group exhibited decreased rsFC between them. These findings highlight a specific alteration in functional connectivity in the DMN in patients with SOC, and provide new insights into the dysfunctional brain organization of different mental disorders.