Doxorubicin-chemotherapy can lead to serious cardiac side effects in cancer-patients, culminating in heart failure. Cardiac oxidative stress and impaired energetics are hypothesized to be at the core of this toxicity. We established a clinically relevant rat model of doxorubicin-induced heart failure characterized with CINE MRI by decreased cardiac function. We show here that these functional changes are preceded by a shift from oxidative to anaerobic glucose metabolism measured with hyperpolarized MRS. These changes are likely due to a loss and impairment of mitochondria, which cannot be alleviated with the mitochondrially targeted antioxidant, MitoQ.