Objective: To establish the incidence and factors associated with hospital-acquired hyponatremia in pediatric surgical patients who received hypotonic saline (sodium 40 mmol/L plus potassium 20 mmol/L) at the rate suggested by the Holliday and Segar's formula for calculations of maintenance fluids. Design: Prospective, observational, cohort study. Setting: Pediatric intensive care unit. Patients: Eighty-one postoperative patients. Interventions: None. Measurements and Main Results: Incidence and factors associated with hyponatremia (sodium <= 135 mmol/L). Univariate analysis was conducted post surgery at 12 hrs and at 24 hrs. Mean values were compared with independent t test samples. Receiver operating characteristics curve analysis was performed in variables with a p<.05, and relative risks were calculated. Eighty-one patients were included in the study. The incidence of hyponatremia at 12 hrs was 17 (21%) of 81 (95% confidence interval, 3.7-38.3); at 24 hrs, it was was 15 (31%) of 48 (95% confidence interval, 11.4-50.6). Univariate analysis at 12 hrs showed that hyponatremic patients had a higher sodium loss (0.62 mmol/kg/hr vs. 0.34 mmol/kg/hr, p = .0001), a more negative sodium balance (0.39 mmol/kg/hr vs. 0.13 mmol/kg/hr, p<.0001), and a higher diuresis (3.08 mL/kg/hr vs. 2.2 mL/kg/hr, p = .0026); relative risks were 11.55 (95% confidence interval, 2.99-44.63; p = .0004) for a sodium loss >0.5 mmol/kg/hr; 10 (95% confidence interval, 2.55-39.15; p = .0009) for a negative sodium balance >0.3 mmol/kg/hr; and 4.25 (95% confidence interval, 1.99-9.08; p = .0002) for a diuresis >3.4 mL/kg/hr. At 24 hrs, hyponatremic patients were in more positive fluid balance (0.65 mL/kg/hr vs. 0.10 mL/kg/hr, p = .0396); relative risk was 3.25 (95% confidence interval, 1.2-8.77; p = .0201), for a positive fluid balance >0.2 mL/kg/hr. Conclusions: The incidence of hyponatremia in this population was high and progressive over time. Negative sodium balance in the first 12 postoperative hours and then a positive fluid balance could be associated with the development of postoperative hyponatremia. (Pediatr Crit Care Med 2010;11:479-483)