Doxorubicin (DOX), an anti-cancer drug, causes a dose-dependent cardiotoxicity. Some evidence suggests that female children have an increased risk for DOX-mediated cardiac damage. To determine if the iron chelator Dexrazoxane (DXR) could reduce DOX-induced cardiotoxicity in the young we injected day 10 neonate female and male rat pups with a single dose of saline or DOX, DXR or DXR+DOX (20:1 ratio). We followed body weight gain with growth, measured cardiac hypertrophy after a 2-week swim exercise program, markers of apoptosis (Bcl-2, Bax, BNIP1, caspase 3 activation), oxidative stress (heme oxygenase 1, protein carbonyl levels), the chaperone protein Clusterin, and the transcriptional activator Egr-1 in hearts of non-exercised and exercised rats on neonate day 38. All DOX-alone and DXR+DOX-treated rats showed decreased weight gain with female rats affected earlier than male rats. DXR-alone, DOX-alone and DXR+DOX treated rats had an increased heart to body weight (HW/BW) ratio after the exercise program with female rats showing the largest increase in HW/BW. Drug-treated females also showed increased cardiac apoptosis, as measured by the increased expression of the pro-apoptotic proteins Bax and BNIP1 and the appearance of caspase 3 activation products, and oxidative stress, as measured by increased heme oxygenase 1 expression, and reduced Egr-1 and Clusterin expression when compared to the similarly treated male rats. We conclude that DXR pre-injection did not reduce DOX-induced non-cardiac and cardiac damage and that young female rats were more susceptible to DXR and DOX toxicities than age-matched male rats.