In this study, we describe two unrelated patients presenting with fatal infantile cardiomyopathy, lactic acidosis and respiratory failure, with severe multiple OXPHOS deficiency and who both harboured an unreported AARS2 variant (c.1738C>T, p.Arg580Trp) in trans with a loss-of-function AARS2 variant, but not the recurrent p.Arg592Trp founder mutation. This evidence concerns the gene AARS2 and respiratory failure.