The rapid increase in mitochondria (MITO) oxidative capacity at birth is initiated by increased oxygen availability and hormone surges, although the signal transduction mechanism(s) remain obscure. Tissue cAMP is elevated at birth in response to hormone surges. While several MITO proteins are targets for cAMP dependent protein kinase A (PKA) the effect on O2 consumption (QO2) by MITO's from newborns has not been evaluated. Preterm rabbit pups were delivered by csection and maintained under normoxia (21% O2, NOX) or hypoxia(10% O2, HYPOX) for 4 hours, or sacrificed at birth (time zero, TZ). Liver MITO's were isolated, incubated in the absence or presence of 100 uM cAMP 7 pU of PKA catalytic subunit, and QO2 determined. Under control conditions site 1(malate pyruvate ADP) dependent QO2 was higher (p < 0.05) in NOX (15.3± 3 nmol O2 / min / mg protein) compared to TZ (7.3 ± 2.8) or HYPOX (10.6 ± 2.1) litter mates. Site 2 (succinate ADP) dependent QO2 was higher (p < 0.05) in both NOX (25.3 ± 6.5) and HYPOX (20.6± 5.5) compared to TZ (10.6 ± 4.4). When isolated MITO's were incubated with cAMP PKA, site 1 QO2 was further increased in NOX (from 15.3± 3 to 21.0 ± 5, p < 0.05) but not HYPOX or TZ preparations. cAMP PKA had no effect on site 2 QO2 in any group. In contrast, when MITO's from 2 wk old pups were evaluated, cAMP PKA reduced site 1 QO2 (from 5.1± 0.8 to 2.9 ± 0.8, nmol O2 / min / ms protein p < 0.05) but had no effect on site 2 site 2 QO2. To determine whether increased QO2 at birth is initiated by beta adrenergic receptor stimulated cAMP pups were treated with 100 ug propranolol (PROP) at birth and maintained under NOX conditions for 4 hours. However, PROP had no effect on MITO QO2 compared to saline treated controls. Taken together these data demonstrate that intact MITO site 1 QO2 is developmentally regulated by cAMP dependent PKA and O2 availability but suggest that increased QO2 at birth is not due to catecholamine surge. The role of insulin/glucagon in PKA modulation of MITO QO2 remains to be determined.