Chemotherapy cocktails containing doxorubicin produce irreversible cardiotoxic side effects that may progress to heart failure, which can only be avoided through dose limitation of the chemotherapeutic agents. Increasing evidence suggest that cardiac dysfunction caused by doxorubicin is triggered by an energetic deficit and alterations in mitochondrial metabolism. We quantified metabolic changes in vivo in a mouse model of acute doxorubicin-induced cardiotoxicity using hyperpolarized 13C MRS.