This study aimed to show the feasibility of using the phosphorescence oxygen analyzer to screen for clinical disorders with impaired cellular bioenergetics. [O(2)] was determined as function of time from the phosphorescence decay of Pd (II) meso-tetra-(4-sulfonatophenyl)-tetrabenzoporphyrin. In sealed vials, O(2) consumption by peripheral blood mononuclear cells was linear with time, confirming its zero-order kinetics. Cyanide inhibited O(2) consumption, confirming the oxidation occurred in the mitochondrial respiratory chain. The rate of respiration (mean±SD, in μM O(2) per min per 10(7) cells, set as the negative of the slope of [O(2)] vs. t) for adults was 2.1±0.8 (n=18), for children 2.0±0.9 (n=20), and for newborns (umbilical cord samples) 0.8±0.4 (n=18), p<0.0001. For an 8-year-old patient with reduced NADH dehydrogenase and pyruvate dehydrogenase activities in the muscle, the rate was 0.7±0.2 (n=3) μM O(2) per min per 10(7) cells. For a 3-month-old patient with hepatocerebral mitochondrial DNA depletion syndrome (MDS) with confirmed mutations in the MPV17 gene, the rate was 0.6μM O(2) per min per 10(7) cells. For an18 month-old patient with MDS and confirmed mutations in the POLG gene, the rate was 0.5 μM O(2) per min per 10(7) cells. For a 6-year-old patient with MDS and confirmed mutations in the POLG gene, the rate was 0.6 μM O(2) per min per 10(7) cells. For 1-week-old patient with congenital lactic acidemia and hypotonia (confirmed mutations in DLD gene), the rate was 1.5 μM O(2) per min per 10(7) cells. For three siblings (9-year-old male, 8-year-old male and 2-month-old female) with congenital progressive myopathy, the rates were 0.9, 0.6 and 1.2 μM O(2) per min per 10(7) cells, respectively. Four patients with congenital lactic acidemia (with inadequate work-up) were also studied; their rates were 0.2, 1.5, 0.3 and 1.7 μM O(2) per min per 10(7) cells. This novel approach permits non-invasive, preliminary assessment of cellular bioenergetics. Potential applications and limitations of this technique are discussed.