Coenzyme Q (CoQ) is a lipid present in all cell membranes. One of the multiple metabolic functions of CoQ is to transport electrons in the reaction catalyzed by sulfide:quinone oxidoreductase (SQOR), the first enzyme of the oxidation pathway of sulfides (hydrogen sulfide, H 2 S). Early evidence of a defect in the metabolism of H 2 S in primary CoQ deficiency came from yeast studies in  Schizosaccharomyces pombe  strains defective for  dps1  and  ppt1  (homologs of  PDSS1  and  COQ2 , respectively), which have H 2 S accumulation. Our recent studies in human skin fibroblasts and in murine models of primary CoQ deficiency show that, also in mammals, decreased CoQ levels cause impairment of H 2 S oxidation. Patient fibroblasts carrying different mutations in genes encoding proteins involved in CoQ biosynthesis show reduced SQOR activity and protein levels proportional to the levels of CoQ. In  Pdss2   kd / kd   mice, kidney, the only organ clinically affected, shows reduced SQOR levels and downstream enzymes, accumulation of H 2 S, and glutathione depletion.  Pdss2   kd / kd   mice have also low levels of thiosulfate in plasma and urine, and increased C4-C6 acylcarnitines in blood, due to inhibition of short-chain acyl-CoA dehydrogenase. Also in  Coq9   R 239 X   mice, the symptomatic organ, cerebrum, shows accumulation of H 2 S, reduced SQOR, increase in thiosulfate sulfurtransferase and sulfite oxidase, and reduction in the levels of glutathione and glutathione enzymes, leading to alteration of the biosynthetic pathways of glutamate, serotonin, and catecholamines.  Coq9   R 239 X   mice have also reduced blood pressure, possible consequence of H 2 S-induced vasorelaxation. Since liver is not clinically affected in  Pdss2  and  Coq9  mutant mice, the effects of the impairment of H 2 S oxidation in this organ were not investigated, despite its critical role in metabolism. In conclusion,  in vitro  and  in vivo  studies of CoQ deficient models provide evidence of tissue-specific H 2 S oxidation impairment, an additional pathomechanism that should be considered in the understanding and treatment of primary CoQ deficiency.