Growing evidence from neuroimaging studies has reported deficits in circuit connectivity between several regions involved in emotional processing, including the prefrontal cortex, amygdala, and midline thalamus in people with schizophrenia and bipolar disorder. These deficits are hypothesized to contribute to circadian and mood disruption experienced by people living with these conditions. Human postmortem studies consistently indicate cell deficits in schizophrenia (SZ) and bipolar disorder (BD), and postmortem proteomic analysis and genome-wide expression analyses report dysregulation in proteins and genes related to myelination and oligodendrocyte metabolism in the thalamic tissues of people with SZ. Together, previous research indicates oligodendrocyte dysfunction in the thalamus could be implicated in SZ and BD symptomatology. The present studies focus on the paraventricular thalamic nucleus (PVT), a small dorsal subnucleus containing numerous thalamic outputs to the prefrontal cortex, amygdala, suprachiasmatic nucleus, and nucleus accumbens. The PVT has been shown to play a role in circadian food timing cues, wakefulness and motivation and is dysregulated in anxiety disorder, substance use disorder, and eating disorders. As a first step in efforts to identify specific cells and molecular pathways behind connectivity deficits, we focus on myelin oligodendrocyte specific protein immunoreactive (MOSP-IR) oligodendrocytes using high resolution quantitative microscopy on human postmortem brain samples. Oligodendrocytes play a fundamental role in sustaining myelin integrity throughout adulthood, and alterations in oligodendrocyte populations could critically impact thalamocortical connectivity in SZ and BD. In order to determine whether oligodendrocytes are decreased in the PVT in SZ and BD, we quantified MOSP-IR oligodendrocytes in post-mortem human tissue using immunohistochemical staining and quantitative stereology-based sampling with light microscopy. We collected whole thalamic specimens of control (n=19), subjects with SZ (n=16), and subjects with BD (n=15), and performed immunohistochemistry to quantify the number of MOSP-IR oligodendrocytes in the paraventricular thalamic nucleus. Fluorescent double-immunohistochemistry was employed to determine the glial identity and differentiation stage of the cells stained. Quantitative stereological sampling was employed to estimate total numbers and numerical densities of MOSP-IR oligodendrocytes in the human PVT. Information from donors’ health records, including exposure to medication, smoking and alcohol use history, as well as information such as post-mortem interval, age, sex, and brain weight were used for statistical analyses to control for confounding factors. We hypothesized that the numbers of MOSP-IR oligodendrocytes in the PVT of people with SZ and BD would be significantly reduced. Our data show decreased MOSP-IR oligodendrocyte numerical density in the PVT of subjects with SZ (p=0.02) and subjects with BD (p=0.03) with strong effect sizes of g= 0.84 and g=0.97, respectively. These data suggest that reduction of MOSP-IR oligodendrocytes in the PVT contribute to decreased oligodendrocyte populations and myelination, impacting thalamic connectivity with critical cortical and subcortical regions involved in psychiatric disorders. These findings raise questions on the mechanisms leading to mature oligodendrocyte decreases. Future experiments to determine MOSP-IR differentiation and migration patterns will investigate whether and how MOSP-IR oligodendrocytes develop and function in the PVT. Additional studies will examine the relationship of mature oligodendrocyte cell numbers with immature oligodendrocytes to determine how myelin deficits are associated with oligodendrocyte dysfunction.