Aim: To evaluate the association between C-reactive protein (CRP) levels and the periodontal status of hemodialysis (HD) patients. Methods: 41 HD patients on rHuEPO therapy were enrolled in the study. Hematologic and biochemical parameters and CRP levels were recorded. The plaque index, gingival index, probing pocket depth and periodontal disease index were used to identify periodontal disease. The patients were divided into 2 groups: group 1 (n = 21), high CRP, and group 2 (n = 20), normal CRP. Results: After periodontal therapy, while the mean CRP level and erythrocyte sedimentation rate declined from 30.46 to 10.36 (p = 0.001) and from 93.4 to 35.8 mg/l (p = 0.001), respectively, the hemoglobin level increased from 9.4 to 10.6 g/dl (p = 0.009) and hematocrit level from 28.2 to 32.0% (p = 0.008) in group 1. Conclusion: Periodontitis is an important and occult source of chronic inflammation and increases the CRP levels in HD patients. Periodontitis can cause hyporesponsiveness to rHuEPO treatment and decrease the hemoglobin levels.