Abstract Purpose We wanted to identify modifiable risk factors for intensive care unit (ICU)–acquired hypernatremia. Materials and Methods We retrospectively studied sodium and fluid loads and balances up to 7 days prior to the development of hypernatremia (first serum sodium concentration, [Na+], >150 mmol/L; H) vs control (maximum [Na+] ≤150 mmol/L; N), in consecutive patients admitted into the ICU with a normal serum sodium (<145 mmol/L) and without cerebral disease, within a period of 8 months. Results There were 57 H and 150 N patients. Severity of disease and organ failure was greater, and length of stay and mechanical ventilation in the ICU were longer in H (P < .001), with a mortality rate of 28% vs 16% in N (P = .002). Sodium input was higher in H than in N, particularly from 0.9% saline to dissolve drugs for infusion and to keep catheters open during the week prior to the first day of hypernatremia (P < .001). Fluid balances were positive and did not differ from N on most days in the presence of slightly higher plasma creatinine and more frequent administration of furosemide, at higher doses, in H than in N. Conclusions High sodium input by 0.9% saline used to dilute drugs and keep catheters open is a modifiable risk factor for ICU-acquired H. Dissolving drugs in dextrose 5% may partially prevent potentially harmful sodium overloading and H.