Neuroimaging and post-mortem studies have implicated altered myelin integrity and oligodendrocyte abnormalities in the dysfunction of neuronal network in schizophrenia, including the prefrontal cortex, Brodmann area (BA) 10. Pyramidal neurons in layer 5 of BA10 are the important link of reciprocal frontal cortical-basal ganglia-thalamic circuits altered in schizophrenia. Previously, we found ultrastructural dystrophic and degenerative alterations of oligodendrocytes in layer 5 of BA10 in schizophrenia. The aim of the study was to estimate the numerical density (Nv) of oligodendrocytes in layer 5 of BA10 in schizophrenia as compared to normal controls. 17 chronic schizophrenia subjects and 22 healthy matched controls were studied in Nissl-stained sections using optical disector method. Group differences were analyzed using ANCOVA followed by post hoc Duncan's test. The Nv of oligodendrocytes was significantly lower (- 32%, p < 0.001) in the schizophrenia group as compared to the control group. Young controls (age < 50 years old) showed significantly higher Nv of oligodendrocytes as compared to elderly controls (age > 50 years old). Young and elderly schizophrenia subgroups did not differ significantly. Both control subgroups have significantly higher Nv of oligodendrocytes as compared to the schizophrenia subgroups. Decreased Nv of oligodendrocytes found in layer 5 of BA10 may be the result of dystrophic and destructive alterations and/or disrupted development of oligodendrocytes in schizophrenia.