Background: Medication-related osteonecrosis of the jaw (MRONJ) is a condition that can occur primarily in patients undergoing or have previously undergone therapy with bisphosphonates, particularly in the presence of risk factors, such as tooth extraction (TE). Purpose: This study aimed to evaluate the effect of selenium (SEL) administration on the prevention of osteonecrosis of the jaw in an MRONJ animal model. Study Design, Setting, and Sample: This study was a longitudinal in vivo animal study using a TE model in a sample of 48 Wistar rats. Predictor Variable: The predictor variables were SEL exposure, timing of SEL exposure, and zoledronic acid (ZOL) exposure. The animals were randomly assigned to 4 treatment groups (n = 12 per group): 1) saline (negative control), 2) ZOL (positive control), 3) SELpreop + ZOL, and 4) ZOL + SELpostop. The animals were administered saline (negative control) or ZOL (0.06 mg/kg, intraperitoneally) once a week for 5 weeks. All rats underwent TE at the end of the fifth week. SEL (0.3 mg/kg, intraperitoneally) was administered once daily for 15 days to the SELpreop + ZOL group before TE and to the ZOL + SELpostop group after TE. All animals were sacrificed at the end of the ninth week. Main Outcome Variables: The primary outcome variables were new bone area, necrotic bone area, fibrosis, new connective tissue formation, and inflammatory cell infiltration in the histopathological analysis, as well as angiogenesis and percentage of osteoblasts in the immunohistochemical analysis. Covariates: There was none. Analyses: Statistical analysis was conducted using the Kruskal–Wallis test, followed by post hoc Bonferroni-corrected Mann–Whitney U tests, with a significance level of P ≤.05. Results: The new bone area was higher in the ZOL + SELpostop group (3.00 score) than in the saline group (0.58 ± 1.08 score, P <.001) and the ZOL group (0.82 ± 1.40 score, P =.001), while the necrotic bone area was lower in the ZOL + SELpostop group (0.08 ± 0.29 score) than in the ZOL group (2.82 ± 0.40 score, P <.001) and the SELpreop + ZOL group (1.67 ± 0.89 score, P =.007). The percentage of osteoblasts was higher in the ZOL + SELpostop group (18.73%) than in the saline group (8.63%, P <.001) and the ZOL group (0.07%, P <.001), and it was also higher in the SELpreop + ZOL group (18.49%) than in the ZOL group (0.07%, P <.001). Conclusion and Relevance: In conclusion SEL prevents MRONJ, with postoperative SEL demonstrating greater prevention effects. Given these findings, we hypothesize that SEL exposure may decrease the risk of MRONJ.