In this study, the microstructure near the metal-oxide interface of a Zr-2.5Nb alloy is characterized after 567 days of exposure to high temperature heavy water with neutron irradiation in a test reactor. The oxides formed in-reactor look distinctly different from those formed in a non-irradiated environment. Specifically, reactor oxides have a more complex microstructure with shorter columnar grains and lateral cracks are a common feature. Transmission electron microscopy (TEM) was used to investigate the nanoscale, distribution, and connectivity of porosity through the oxide layer. The observed nano-porosity may provide short-circuit pathways for the transport of hydrogen or ions through the film to the metal/oxide or oxide/solution interfaces. Scanning TEM is used to provide complementary chemical information. Energy-dispersive X-ray spectroscopy analysis revealed differences in Nb segregation in the oxide between irradiated and non-irradiated samples. Multiple linear least squares (MLLS) fitted electron energy loss spectroscopy (EELS) maps showed the existence of a Widmanstätten-type, equiaxed, and thin plate morphology of metastable h-ZrO (15.4 eV).