Temporal lobe epilepsy (TLE) is characterized by distinct neuropathological findings, such as hippocampal sclerosis and reactive astrogliosis. Recently, MRI studies have revealed the presence of white matter pathology in brains of epilepsy patients. The purpose of this study is to evaluate the involvement of oligodendroglia in the epileptogenic process. Using TPPP/p25 as a marker for mature oligodendroglia, we evaluated the hippocampus in 26 surgical specimens from patients with TLE and 9 autopsy controls without neuropathological alterations for changes in oligodendroglial cell densities (mm2) in hippocampal, entorhinal, and temporal white matter, and the amount of perineuronal oligodendrocytes in CA1 subregion. Oligodendrocyte cell densities were significantly elevated in epilepsy patients compared to controls in all four examined white matter subregions. In addition, in the CA1 sector, the percentage of neurons showing more than one perineuronal oligodendrocyte was significantly higher in epilepsy patients. In conclusion, our study expands the glial reactions beyond astrogliosis and shows that prominent oligodendroglial response is a consistent pathological feature characteristic for TLE.