['Cumulative dose-dependent nonischemic cardiomyopathy (NICM) remains a significant risk with the use of some chemotherapeutic agents. In this context, omega-3 polyunsaturated fatty acids (PUFA) have been investigated for their cardioprotective potential in rodent and in\xa0vitro models of anthracycline toxicity, with conflicting results. This study evaluated prophylactic omega-3 PUFA supplementation in a large-animal model of anthracycline-induced NICM.', 'Merino sheep were randomized to oral drenching with omega-3 PUFA (fish oil; n\xa0= 8) or olive oil placebo (n\xa0= 9) 3 weeks before commencing repeated intracoronary infusions of doxorubicin (DOX) to induce cardiac dysfunction. Cumulative DOX dose was 3.6 mg/kg. Drenching was continued for 12 weeks after final DOX exposure. Despite significant increases in tissue omega-3 PUFA levels (P < .05 vs placebo), omega-3-treated sheep displayed greater signs of anthracycline cardiotoxicity than placebo animals, consisting of left ventricular dilatation and a greater decline in ejection fraction (P\xa0<\xa0.05), although myocardial fibrosis burden was similar in both groups.'] Does dietary omega-3 supplementation exacerbate left ventricular dysfunction in an ovine model of anthracycline-induced cardiotoxicity?