Debilitating muscle weakness and fatigue are common symptoms in cancer patients, the underlying cause of which is unknown. Compromised mitochondrial function can lead to persistent weakness in skeletal muscle. To determine if cancer alters skeletal muscle mitochondrial respiratory control/capacity and/or reactive oxygen species (ROS) production, C57BL6 male mice were injected with syngeneic Lewis lung carcinoma cells subcutaneously. Permeabilized fibers were prepared from the red gastrocnemius muscle 30 days post‐injection. Compared to controls, TB mice showed a significant (p<0.05) reduction in both complex I‐linked (mM: 5 glutamate/2 malate) basal (state 4) respiration (−54 ± 8 % change, mean ± SE) and maximal ADP‐stimulated (State 3) respiration (−51 ± 6 %, n=5). To examine the kinetics of complex I mediated respiration, we titrated in glutamate under maximal state 3 conditions. Surprisingly, the Km for glutamate was slightly decreased in TB mice (TB: 2 ± 9, CTRL: 4 ± 1, p<0.05), indicating improved sensitivity. In response to succinate titration during state 4 conditions supported by glutamate, preliminary data suggests mitochondrial H2O2 emitting potential is elevated in skeletal muscle from TB mice (+58 ± 23 %, n=4). Our findings suggest cancer compromises metabolic function in skeletal muscle, leading to a mitochondrial environment that increases the potential for electron leak and ROS generation.Supported by DK 073488