Exercise of sufficient intensity and duration can cause acute oxidative stress. Plasma protein carbonyl (PC) moieties are abundant, chemically stable and easily detectable markers of oxidative stress that are widely used for the interpretation of exercise-induced changes in redox balance. Despite many studies reporting acute increases in plasma PC concentration in response to exercise, some studies, including those from our own laboratory have shown decreases. This review will discuss the differences between studies reporting increases, decreases and no change in plasma PC concentration following exercise in humans; highlighting participant physiology (i.e. training status) and study design (i.e. intensity, duration and novelty of the exercise bout) as the main factors driving the direction of the PC response to exercise. The role of the 20S proteasome system is proposed as a possible mechanism mediating the clearance of plasma PC following exercise. Resting and exercise- induced differences in plasma protein composition and balance between tissues are also discussed. We suggest that exercise may stimulate the clearance of plasma PC present at baseline, while simultaneously increasing reactive oxygen species production that facilitates the formation of new PC groups. The balance between these two processes likely explains why some studies have reported no change or even decreases in plasma PC level post- exercise when other biomarkers of oxidative stress (e.g., markers of lipid peroxidation) were elevated. Future studies should determine factors that influence the balance between PC clearance and formation following acute exercise.