Background Low serum sodium levels have been associated with mortality both in patients with and without chronic kidney disease. In this study, we investigated this association in relation to glycemic control in hemodialysis (HD) patients. Materials and methods Between March and September 2005, 697 prevalent HD patients were enrolled in this prospective observational study and followed up for all-cause and cardiovascular mortality. The associations of serum sodium concentration with both overall and cardiovascular survival rates were studied. Results At baseline, mean predialysis serum sodium concentration was 138.4 +/- 2.3 mEq/L (range: 130145 mEq/L). Mild hyponatremia (< 135 mEq/L) was present in only 41 subjects (5.9%), and no patient had serum sodium level < 130 mEq/L. During 20.2 +/- 6.2 months of follow-up, 119 patients (15.9%) died, 68 from CV causes. In adjusted Cox regression analysis, lowest sodium quartile was associated with 2.13-fold increased risk of overall mortality (95% confidence interval (CI) 1.143.98, P = 0.01, model chi-square 114.6, P < 0.001). As a continuous variable, each 1 mEq/L increase in predialysis sodium concentration was associated with a hazard ratio (HR) of 0.87 for overall mortality (95% CI 0.810.95, P = 0.002) and 0.86 for cardiovascular mortality (95% CI 0.780.96, P = 0.007). The predictivity of low serum sodium was prominent in diabetic subjects but not in nondiabetics. However, relationship between serum sodium and patient survival in diabetics was lost after adjustment for the HbA1c level: HR 0.91 (95% CI 0.781.05, P = 0.20). Conclusions Low serum sodium concentration is associated with mortality only in those with diabetes. Furthermore, the impact of serum sodium on survival in these patients seems to be derived from poor glucose control.