Background: In surgical patients, hypoalbuminemia may occur as a component of acute-phase response (APR) syndrome, which we hypothesized could decrease serum sodium levels. Aim: To compare the frequency of hyponatremia in adult surgical inpatients with or without APR syndrome. Methods: All the simultaneous plasma sodium and albumin results (n = 168), obtained from adults in surgical wards and corresponding to a 6-month period, were searched in the hospital mainframe. Other relevant laboratory and clinical data were also registered. APR was ascertained by the presence of major physical trauma, surgery or infection, plus hypoalbuminemia (serum albumin <3.5 g/dl) and neutrophil left shift (≥7% of band count) associated with peripheral leukopenia (white blood cells <4,000/mm<sup>3</sup>) or leukocytosis (WBC >9,000/mm<sup>3</sup>). Hyponatremia was defined by serum sodium concentration <135 mEq/l. Results: APR-positive patients (n = 113) had lower blood hemoglobin (10.92 ± 2.18 vs. 13.53 ± 2.30 g/dl), and serum albumin levels (median, range: 2.8, 1.9–3.4 vs. 3.7, 3.5–4.2 g/dl) than APR-negative (n = 55) ones, the same occurring in relation to antibiotics (54.8 vs. 10.9%) and intravenous 5% dextrose in water (55.7 vs. 20.0%) or isotonic saline (46.0 vs. 9.1%) infusion. The hyponatremia frequency was higher among APR-positive patients (31.0 vs. 10.9%). Conclusion: The higher percentage of hyponatremia among APR-positive patients could be attributed to decreased serum albumin levels associated with APR.