Persistent periapical lesions (PPL) are the result of pulpar necrosis induced by bacterial infection resulting in bone degradation and culminating with the loss of dental piece. Pathological changes in the peripapice are associated with the presence of free radicals. The transcription factor Nrf2 is the main regulator of the endogenous antioxidant response against oxidative stress and has been implicated in the regulation of osteoclastogenesis.The aim is to determine the oxidative condition in samples from patients with Persistent Periapical Injuries as a detonating factor of tissue damage. An observational, descriptive, cross-sectional study was carried out in samples with PPL (cases) and samples by removal of third molars (controls) obtained in the clinic of the specialty in endodontics, University of Guadalajara. Samples were submitted to histological staining with Hematoxylin-Eosin, lipoperoxide analysis, Superoxide Dismutase (SOD), Glutathione-Peroxidase (GPx) and Catalase (CAT) activities were determined by immunoenzymatic assays and NrF2 by Western Blot analysis. Samples from PPL patients histologically showed an increased presence of lymphocytes, plasma cells, and eosinophils, as well as a decrease in extracellular matrix proteins and fibroblast cells. There was a rise in lipid peroxidation, GPx and SOD activities, but an important decline (36%) in Catalase activity was observed (p<0.005); finally, NrF2-protein was diminished at 10.41%. All comparisons were between cases vs controls. The alterations in antioxidants endogenous NrF2-controlled are related to osseous destruction in patients with PPL.