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Dilated cardiomyopathy (DCM) has an estimated prevalence of 1 in 250 in the UK and is characterised by enlargement and dilation of one or both of the heart ventricles. This impairs the contractility of the heart and affects its ability to pump blood, resulting in a left ventricular ejection fraction of less than 40%. Efficient energy metabolism is a fundamental process in cardiac maintenance, and it requires a high ATP turnover to achieve optimal contractile function. Given that mitochondrial function is closely linked to the development of DCM, disruption to energy metabolism pathways can impair cardiomyocyte function.A homozygous pathogenic variant, p.R253W SLC5A6, was identified in a family where two siblings presented with DCM. SLC5A6 encodes the Sodium-dependent Multivitamin Transporter, a transmembrane protein that is crucial for facilitating the active transport of three vitamins: biotin, pantothenic acid and lipoic acid; all of which are critical, organic enzyme cofactors required for energy metabolism in the mitochondria.A conditional cardiac-specific mouse model of Slc5a6 (Slc5a6cKO) was engineered to study DCM progression and phenotype rescue using vitamin supplementation.Slc5a6cKO mice presented with a cardiomyopathy phenotype and sudden death from 20 weeks. Slc5a6cKO mice displayed abnormal ECG parameters from 6 weeks, and the hearts showed fibrosis and abnormal mitochondrial morphology. Proteomic analysis revealed dysregulated pathways associated with energy metabolism, particularly fatty acid-beta oxidation, prior to disease presentation. Dietary supplementation with biotin and pantothenic acid prevented premature death in Slc5a6cKO mice. Cardiac conduction and function were restored, and mitochondrial structure and protein expression profiles were also normalised.These findings demonstrate that a lethal mouse model of DCM can be successfully treated with vitamin supplementation to prevent mitochondrial defects and progression to cardiomyopathy.