Mitochondrial Diseases (MD) are disorders of function in cellular oxidative phosphorylation caused by diverse nuclear DNA and mtDNA mutations and seen in 1/5,000 births. The purpose of this study was to examine relationships across medical indices, biochemical measures, and neurobehavioral functioning in children with MD. Findings from Western Blot, Native Gels, High Resolution Respirometry, and the Nijmegen diagnostic criteria were assessed in relation to children’s processing speed and attention, based on the prediction that impaired functioning of proteins, complexes, and cellular respiration, that are critical in ATP production, will impact neurodevelopment and related neuropsychological processes in children with MD. Twenty-five children (ages 4-13) were administered subtests from the DAS-II and NEPSY-II. Results from multiple regression analyses suggest that processing speed and attention deficits may be markers of abnormal protein expression that interferes with the production of ATP in the oxidative phosphorylation process; implications for future research are presented.