Unaccustomed exercise is known to produce strength loss, soreness, and myocellular disruption. With repeated exercise stimuli, these muscle damage markers are attenuated, producing the so-called repeated bout effect. No direct connection have been established between this repeated bout effect and exercise-induced increases in protein turnover, but it appears that a degree of tolerance is developed towards exercise for both. The present study sought to investigate markers of protein degradation by determining the expression of components related to the ubiquitin-proteasome system with repeated exercise bouts. Healthy males carried out 30 min of bench stepping, performing eccentric work with one and concentric work with the other leg (n=14), performing a duplicate exercise bout 8 weeks later. A non-exercising control group was included (n=6). RNA was extracted from muscle biopsies representing time points PRE, +3 hours, +24 hours and +7 days, and selected mRNA species were quantified using Northern blotting. The exercise model proved sufficient to produce a repeated bout effect in terms of strength and soreness. For FOXO1 and MURF1, strong upregulations were seen exclusively with concentric loading (p<0.001), while Atrogin-1 displayed a strong downregulation exclusively in response to eccentric exercise (p<0.001). For MURF1 transcription, the first bout produced a downregulation that persisted until the second bout (p<0.01). In conclusion, the ubiquitin-proteasome system (UPS) is modulated differentially in response to varying loading modalities and with different time frames in a way that to some extent reflects changes in protein metabolism known to take place with exercise.