Abstract Body: BACKGROUND: The renin-angiotensin-aldosterone system (RAAS) plays an important role in blood pressure (BP), electrolyte balance, and fluid volume regulation. High salt diets suppress both RAAS and fasting beta-hydroxybutyrate (β-OHB), the primary ketone produced in the body. Recent findings suggest nutritional ketosis increases circulating aldosterone concentrations. However, the interaction between high salt and dietary ketones on RAAS remains to be investigated. Therefore, we examined the effects of short-term high salt and ketone supplementation on RAAS in healthy adults. METHODS: Thirteen adults (10 M/3 F, age 27 5 years, BMI: 25 3 kg/m²; mean SD) participated in this randomized, crossover study consisting of three 10-day conditions: A) low salt: dextrose capsules and placebo drink; B) high salt: salt capsules and placebo drink; and C) high salt + ketone: salt capsules and ketone drink. Participants were instructed to eat a low sodium (0.8 mg/kcal/day) diet for all conditions and take salt capsules to increase total sodium consumption to 2 mg/kcal/day for salt loading. Ketone monoester drinks provided 36 g β-OHB/day. We assessed resting BP, 24-hour urinary electrolyte excretion (sodium, potassium, chloride), plasma renin activity, and serum aldosterone concentration. Depending on data normality, repeated measures ANOVA or Friedman test with mean SD or median(IQR) are reported with α set at ≤0.05. RESULTS: Resting BP (systolic/diastolic) was unchanged across conditions (low salt: 110/65 10/5, high salt: 110/65 17/9, high salt + ketone: 108/64 8/6 mmHg, p=0.95). Sodium excretion increased with salt loading (low salt: 108 52, high salt: 170 75, high salt + ketone: 195 137 mmol/day, p=0.03). Potassium and chloride excretion were unchanged (ps≥0.76). Plasma renin activity did not differ across conditions (low salt: 1.35(0.84), high salt: 0.50(1.10), high salt + ketone: 1.14(0.90) ng/ml/hr, p=0.16). However, serum aldosterone was suppressed by salt loading (low salt: 22.01 13.75, high salt: 10.95 7.02, high salt + ketone: 10.28 3.29 ng/ml, p=0.01) with no difference between the high salt and high salt + ketone conditions (p=0.71). CONCLUSION: Our preliminary data suggest ketone supplementation does not influence the effects of high dietary salt on circulating renin activity and aldosterone. A larger sample including salt-sensitive adults is needed to confirm our findings.