There is increasing evidence to support the notion that oligodendrocyte and myelin abnormalities may contribute to the functional dysconnectivity found in the major psychiatric disorders. The putamen, which is an important hub in the cortico-striato-thalamo-cortical loop, has been implicated in a broad spectrum of psychiatric illnesses and is a central target of their treatments. Previously we reported a reduction in the numerical density of oligodendrocytes and oligodendrocyte clusters in the prefrontal and parietal cortex in schizophrenia. Oligodendrocyte clusters contain oligodendrocyte progenitors and are involved in functionally dependent myelination. We measured the numerical density (Nv) of oligodendrocytes and oligodendrocyte clusters in the putamen in schizophrenia, bipolar disorder (BPD) and major depressive disorder (MDD) as compared to healthy controls (15 cases per group). Optical disector was used to estimate the Nv of oligodendrocytes and oligodendrocyte clusters. A significant reduction in both the Nv of oligodendrocytes (- 34%; p < 0.01) and the Nv of oligodendrocyte clusters (- 41%; p < 0.05) was found in the schizophrenia group as compared to the control group. Sexual dimorphism for both measurements was found only within the control group. The Nv of oligodendrocytes was significantly lower in male schizophrenia cases as compared to the male control cases. However, the Nv of oligodendrocyte clusters was significantly lower in all male clinical cases as compared to the male control group. The data suggest that lowered density of oligodendrocytes and oligodendrocyte clusters may contribute to the altered functional connectivity in the putamen in subjects with schizophrenia.