Muscle tissue may be damaged following intense prolonged training as a consequence of both metabolic and mechanical factors. Serum levels of skeletal muscle enzymes or proteins are markers of the functional status of muscle tissue, and vary widely in both pathological and physiological conditions. Creatine kinase, lactate dehydrogenase, aldolase, myoglobin, troponin, aspartate aminotransferase, and carbonic anhydrase CAIII are the most useful serum markers of muscle injury, but apoptosis in muscle tissues subsequent to strenuous exercise may be also triggered by increased oxidative stress. Therefore, total antioxidant status can be used to evaluate the level of stress in muscle by other markers, such as thiobarbituric acid-reactive substances, malondialdehyde, sulfhydril groups, reduced glutathione, oxidized glutathione, superoxide dismutase, catalase and others. As the various markers provide a composite picture of muscle status, we recommend using more than one to provide a better estimation of muscle stress.