BackgroundDoxorubicin is a common antineoplastic agent with dose‐dependent cardiotoxic adverse effects, and pre‐existing myocardial dysfunction is a contraindication to its use.ObjectivesTo systematically define the hemodynamic and biochemical alterations in dogs undergoing chemotherapy for newly diagnosed lymphoma and assess the reversibility of these alterations with fluid administration.AnimalsTwenty‐one client‐owned dogs with newly diagnosed lymphoma were evaluated 1 week after induction of chemotherapy. Underlying degenerative valve disease was exclusionary. Eighteen healthy age‐ and weight‐matched dogs were used as controls.MethodsPhysical examination, blood pressure by Doppler, echocardiography, and biochemical evaluation (routine serum biochemistry, plasma renin activity and aldosterone concentrations, plasma and urine osmolalities, and urine electrolyte concentrations) were measured in dogs with lymphoma and compared to controls. Dogs with lymphoma received crystalloids IV at 6 mL/kg/h for 24 hours. All variables were reassessed at 4 and 24 hours. Deuterium oxide dilution and bromide dilution were used to determine total body water and extracellular water space, respectively.ResultsBaseline echocardiograms showed significantly smaller chamber dimensions in dogs with lymphoma compared to controls. These changes were reversed by fluid administration. Systolic blood pressure and urine sodium concentration were significantly increased, and bromide dilution space, PCV, urine specific gravity, and urine potassium concentration were significantly decreased compared to controls.Conclusion and Clinical ImportanceEchocardiographic and biochemical abnormalities in dogs with lymphoma appear consistent with volume depletion, and may be the result of systemic hypertension and subsequent pressure natriuresis.