High dietary salt intake is an important risk factor for cardiovascular and renal diseases. However, sexual disparity exists in the response of target organs to high salt diet (HSD). To determine how sex affects cardiac and renal functions' response to HSD, 20 weanling Sprague-Dawley rats (10 males and 10 females) were divided into 4 groups of 5 rats each. The rats were fed a normal diet (0.3% NaCl) or HSD (8% NaCl) for 12 weeks. Fluid balance (FB) was determined from 24 hrs water intake and voided urine. Blood pressure (BP) was measured via arterial cannulation under anesthesia (25% w/v urethane and 1% w/v α-chloralose; 5 ml/kg, i.p). Serum levels of troponin I, aminotransaminases, creatinine, urea, uric acid and electrolytes as well as urinary concentration of albumin, creatinine, and electrolytes were measured using appropriate assay kits. Values are presented as mean ± S.E.M, compared by two-way ANOVA and Bonferroni post Hoc test. In the male rat, HSD significantly increased BP, serum: Troponin I, LDH and sodium (p < 0.05), urinary: albumin, sodium, potassium and FB (p < 0.05). In the female rat, HSD increased BP, serum: troponin I, LDH, sodium and creatinine clearance (p < 0.05), urinary: albumin, sodium and potassium (p < 0.01). However, HSD increased more, the BP, serum: Troponin I, LDH, urinary albumin and FB in male rats, while HSD increased urinary sodium more in female rats. Basal values in male vs. female of serum LDH and urinary albumin were significantly different. Thus, sex plays an important role in the response of the heart and kidney to salt stress.