Leigh Syndrome French Canadian (LSFC) is a rare autosomal recessive metabolic disorder characterized by severe lactic acidosis crises and early mortality. LSFC patients carry mutations in the Leucine Rich Pentatricopeptide Repeat Containing (LRPPRC) gene, which lead to defects in the respiratory chain complexes and mitochondrial dysfunction. Mitochondrial respiration modulates cellular metabolic activity, which impacts many cell types including the differentiation and function of immune cells. Hence, we postulated that, in addition to neurological and metabolic disorders, LSFC patients may show impaired immune activity. To gain insight into the quality of the immune response in LSFC patients, we examined the response to the measles, mumps and rubella (MMR) vaccine by measuring antibody titers to MMR in the plasma. In a cohort of eight LSFC patients, the response to the MMR vaccine was variable, with some individuals showing antibodies to all three viruses, while others had antibodies to two or fewer viruses. These results suggest that the mutations in the LRPPRC gene present in LSFC patients may affect the immune response to vaccines. Monitoring vaccine response in this fragile population should be considered to ensure full protection against pathogens.