The purpose of this investigation was to examine the influence of short-term intense endurance training on cycling performance, along with the acute and chronic signaling responses of skeletal muscle stress and stability markers. Ten recreationally active subjects (25 ± 2 yr, 79 ± 3 kg, 47 ± 2 ml·kg·min-1) were studied before and after a 12-day cycling protocol to examine the effects of short-term intense (70-100% VO2max) exercise training on resting and exercise-induced regulation of molecular factors related to skeletal muscle cellular stress and protein stability. Skeletal muscle biopsies were taken at rest and 3h following a 20 km cycle time trial on days 1 and 12 to measure mRNA expression and protein content. Training improved (p<0.05) cycling performance by 5 ± 1%. Protein oxidation was unaltered on day 12, while resting SAPK/JNK phosphorylation was reduced (p<0.05), suggesting a reduction in cellular stress. The maintenance in the myocellular environment may be due to synthesis of cytoprotective markers along with enhanced degradation of damage proteins, as training tended (p<0.10) to increase resting protein content of MnSOD and HSP70, while mRNA expression of MuRF-1 was elevated (p<0.05). Following training (day 12), the acute exercise-induced transcriptional response of TNF-α, NFB, MuRF-1, and PGC1α was attenuated (p<0.05) compared to day 1. Collectively, these data suggest that short-term intense training enhances protein stability, creating a cellular environment capable of resistance to exercise-induced stress, which may be favorable for adaptation