Purpose: To quantify the effect of sodium selenite (selenium) on radiation-induced oral mucositis (mouse) after subcutaneous or topical administration. Material and Methods: Mucosal ulceration of the lower epithelium of mouse tongue was analyzed. Selenium (5 μg) was applied subcutaneously (s.c.) or locally, 60 min or 30 min prior to irradiation, respectively. In combination with single-dose irradiation, a single selenium application was given. With daily fractionated irradiation (3 Gy/fraction) for 1 week (days 0-4), selenium was administered at all 5 days of irradiation. With ten fractions over 2 weeks, selenium was applied in week 1, week 2, or both. All fractionation protocols were terminated by graded test doses to generate full dose-effect curves. Results: In a single-dose control experiment, the ED ₅₀ (dose after which ulcer induction is expected in 50% of the mice) was 12.9 ± 1.6 Gy. Selenium increased the ED₅₀ to 17.7 ± 2.6 Gy (s.c.; p = 0.0003) and 16.3 ± 3.0 Gy (local; p = 0.0104). The ED₅₀ for test irradiation after 5 x 3 Gy was 7.4 ± 2.2 Gy. Subcutaneous administration of selenium resulted in an ED₅₀ of 11.5 ± 2.0 Gy (p = 0.0015), local application yielded an ED₅₀ of 10.0 ± 2.1 Gy (p = 0.0284). The ED₅₀ for test irradiation after 10 x 3 Gy/2 weeks was 8.0 ± 1.7 Gy. Subcutaneous or local administration of selenium in week 1 yielded a significant increase in ED ₅₀ to 10.5 ± 1.0 Gy (p = 0.0069) and 10.7 ± 1.0 Gy (p = 0.0039), respectively. By clear contrast, selenium administration in week 2 had no significant effect. Administration in both weeks resulted in an ED ₅₀ of 9.1 ± 2.0 Gy (s.c.; p = 0.2747) and 9.7 ± 1.4 Gy (local; p = 0.0541). Conclusion: Administration of sodium selenite during clinically relevant fractionated irradiation protocols has a significant effect during the initial treatment phase, i.e., week 1 in the mouse. Therefore, in clinical radiotherapy, the latent time to manifestation of confluent mucositis may be significantly prolonged, and hence the burden for the patient clearly reduced by selenium.