Here we investigated the metabolic response of rat liver to short-term (2 days) and prolonged (14 days) exposure to inhalation hypoxia (10% O2). The role of the mitochondrial electron transport system in this response, and so the importance of altered respiratory capacity, was probed through the mild inhibition of mitochondrial respiratory complex III. This was achieved through administration of a low dose of known CIII inhibitor GSK932121A through i.p. injection. To investigate the effects of acute suppression of food intake upon hypoxic exposure, we include pair-fed normoxic animals. This allowed us to separate the effects of a reduced food intake from hypoxia per se. We adopted multiple techniques to comprehensively assess the metabolic response to hypoxia, including targeted metabolomics and lipid profiling on snap frozen liver and plasma alongside detailed mitochondrial phenotyping of the liver. This includes evaluation of mitochondrial respiration utilising fresh tissue homogenate, transmission electron microscopy analysis of the mitochondrial network, examination of mitochondrial supercomplex formation using BN-PAGE and gene expression of related regulatory factors. Liver respiratory measures were corrected to tissue wet weight whilst both metabolic and lipidomic profiling data were corrected to protein concentration and internal standard.