AIMS Heart failure (HF) is a major public health issue currently affecting more than 23 million patients worldwide. Hyponatraemia has been shown to be a predictor of poor outcome in patients with acute and chronic HF. Therefore, we aimed at finding a marker for early detection of patients at risk for developing hyponatraemia. To this end, the present study investigated the relationship between initial serum chloride and follow-up sodium levels in acute heart failure (AHF) patients. METHODS AND RESULTS The present study was performed as a prospective, single-centre, observational research with a total of 152 hospitalised AHF patients. Compared to patients with initial normochloraemia, patients with initial hypochloraemia had a statistically significantly higher incidence of hyponatraemia after a 3-month follow-up [P<0.001; odds ratio (OR)=27.08, CI: 4.3-170.7]. A similar finding was obtained upon exclusion of patients with initial hyponatraemia with Fishers test [P=0.034; odds ratio (OR)=15.5, CI:1.7-140.6]. Binary logistic regression revealed a significantly increased in-hospital mortality in the hypochloraemic/normonatriaemic (OR=4.08, CI 1.08-15.43, P=0.039), but not in the hypochloraemic/hyponatraemic, normochloraemic/hyponatraemic or normonatriaemic/normochloraemic patients. Ejection fraction (EF) at admission was significantly higher in hypochloraemic/normonatriaemic, compared to normonatriaemic/normochloraemic patients, but similar to EF in both hypochloraemic/hyponatraemic and normochloraemic/hyponatraemic patients. The N-terminal precursor Brain Natriuretic Peptide (Nt-proBNP) levels at admission were significantly lower in hypochloraemic/normonatriaemic compared to hypochloraemic/hyponatraemic and normonatriaemic/normochloraemic patients, respectively. CONCLUSION The data show that initial low serum chloride concentration is predictive of developing hyponatraemia and associated with increased in-hospital mortality in AHF patients.