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Patients with end-stage renal disease (ESRD) are at an increased risk of cardiovascular disease due to many factors including inflammation and oxidative stress. N-acetylcysteine (NAC) is a thiol-containing anti-oxidant with anti-inflammatory properties. We aimed to assess the effect of three months treatment with oral NAC on the plasma levels of inflammatory mediators like interleukin-6 (IL-6) and C-reactive protein (hs-CRP) in patients on hemodialysis (HD). Twenty-four patients (nine males and 15 females) on maintenance HD were recruited in the study. Their mean age was 55.3 years. All the patients received oral NAC (600 mg twice a day) for a period of three months. The serum levels of biomedical parameters and IL-6 and hs-CRP were measured at baseline and three months after initiation of treatment. A significant decrease in serum levels of hs-CRP (22.4 vs. 5.2), IL-6 (8.1 vs. 3.6), parathyroid hormone (iPTH) (257.2 vs. 158.8), ferritin (632.0 vs. 515.1) and erythrocyte sedimentation rate (ESR) (54.2 vs. 38.3) was observed following NAC treatment. Female subjects presented with a significantly higher change in serum levels of hs-CRP compared with males (23 vs. 5.4). In three subjects who were less than 40 years old, the hs-CRP and IL-6 levels showed an increase following NAC treatment. Our study found that short-term oral NAC treatment might result in the reduction of IL-6 and hs-CRP in patients who are on regular HD. This suggests that patients with ESRD may benefit from the anti-inflammatory effects of NAC.