Objective: To analyze the behavior of pH and sodium bicarbonate (NAHCO3) in the saliva of patients with leukemia during the administration protocol for Methotrexate (Mtx). Materials and Methods: A controlled clinical essay was carried out on 23 patients between 4 and 18 years of age with high-risk Acute Lymphoblastic Leukemia. Sampling was carried out at To : basal condition; T1 : 12 hours after intravenous administration of sodium bicarbonate, before administering Mtx and T2 : 3 hours after administering Mtx, the time of maximum concentration. Chiron-Diagnostic 378® equipment was used to determine pH and sodium bicarbonate. The data was interpreted using Analysis of Variance at the 5% significance level. Results: The highest values of sodium bicarbonate were observed at T2 , with salivary pH levels remaining within neutrality ranges, diminishing slightly in T1 . Conclusion. In this study, the dose of sodium bicarbonate considered in the administration protocol of 3 g /m2 Mtx, kept sodium bicarbonate levels in saliva at normal levels and pH neutral.