Patients with Congestive heart failure (CHF) are very often treated with digoxine (DX; Na/K-ATPase inhibitor) combined with furosemide (FUR; Na/K/2Cl-Cotransporter inhibitor). There are contradictory reports about salivary [Na⁺], [K⁺] and [Cl^-] changes induced by DX or FUR alone, or even about their combination. In the present study, ionic composition in saliva and blood samples from 97 CHF patients (I-II/IV stage) and 58 healthy subjects was analyzed. DX mean dose was 213.3 ± 5 μg.day^-1 and almost all patients received 40 mg.day^-1 of FUR. The mean treatment duration for any drug was 40.15 ± 71.42 weeks. Both groups did not display age or gender distribution differences. All three salivary ions in patients receiving combined treatment were statistically higher than those from the control group [Na⁺] = +40.4% (P = 0.000004), [K⁺] = +24.4% (P = 0.001) and [Cl^-] = +36.9% (P = 0.009) which were not related to gender. No dose-response relationship was found between treatment time and ionic concentration. Results are explained by Na/K-ATPase and Na/K/2Cl Cotransporter locations in both acinar and ductal salivary cells.