Background: Increased oxidative stress in end-stage renal disease is regarded as one of the important mechanisms in the atherosclerosis and muscle wasting. However, studies examining the clinical significance of oxidative stress by direct measurement of these markers and its association with volume status and sarcopenia are limited. Methods: A follow-up cross-sectional study was performed in stable hemodialysis (HD) patients and serum protein carbonyl levels were measured as a biomarker of oxidative stress. Additionally, multi-frequency body composition analysis, handgrip strength (HGS) and nutritional assessments were performed at baseline. Results: Eighty-eight patients undergoing HD were included and 30 (34.1%) patients died during a mean follow-up of 5.2 years. The mean patient age was 60.6 ± 13.5 years, and the mean HD duration was 50.8 ± 41.3 months. In total, 16 patients (18.2%) were overhydrated, 49 (55.7%) had low HGS and 36 (40.9%) had low muscle mass. Serum protein carbonyl levels were associated with serum levels of albumin, prealbumin and transferrin, hydration status and low HGS. Overhydration (odds ratio [OR] 7.01, 95% CI 1.77-27.79, p = 0.006), prealbumin (OR 0.91, 95% CI 0.83-0.99, p = 0.030), subjective global assessment (OR 3.52, 95% CI 1.08-11.46, p = 0.037) and sarcopenia (OR 3.41, 95% CI 1.02-11.32, p = 0.046) were significantly related to increased serum protein carbonyl levels. Multivariate analysis showed that the serum levels of protein carbonyl (Hazard ratio [HR] 2.37, 95% CI 1.02-5.55, p = 0.036), albumin (HR 0.17, 95% CI 0.06-0.46, p = 0.003), prealbumin (HR 0.86, 95% CI 0.80-0.92, p = 0.001), overhydration (HR 2.31, 95% CI 1.26-8.71, p = 0.015) and sarcopenia (HR 2.72, 95% CI 1.11-6.63, p = 0.028) were independent determinants of allcause mortality. Conclusions: Serum protein carbonyl was significantly associated with overhydration, nutritional status and sarcopenia, and could be a new predictor of mortality in patients undergoing HD.