We examined the effects of zinc supplementation on serum zinc and C-reactive protein concentrations in hemodialysis patients. This was a randomized, double-blinded, placebo-controlled clinical trial. This study was conducted at the Shahid Faghihi and Namazi Dialysis Centers in Shiraz, Iran. Fifty-five hemodialysis patients (32 men and 23 women) participated after meeting the following criteria: zinc deficiency, treated for a minimum of 6 months; no record of hospitalizations in the preceding 3 months; and hemodialysis treatment 2 to 3 times per week. Patients were randomly divided into two groups. The zinc supplementation group (n=28) received a 220-mg zinc sulfate capsule, and the control group (n=27) received a placebo capsule (220 mg corn starch), for 42 days. Fasting, predialysis serum samples were collected on days 0 and 42 to determine serum zinc and C-reactive protein levels. After supplementation, subjects in the zinc-supplemented group showed significant increases in serum zinc concentrations, from 57.4+/-2.4 microg/dL SEM on day 0 to 88.4+/-4.8 microg/dL SEM on day 42. Serum C-reactive protein concentrations were initially high among subjects in the control (15.1+/-3.9 mg/L SEM) and zinc-supplemented (13.5+/-3.8 mg/L SEM) groups. Serum C-reactive protein concentrations in the control group increased throughout the study period, but did not reach statistical significance. A progressive decrease in serum C-reactive protein concentrations was observed in the zinc-supplemented group from the beginning (13.5+/-3.8mg/L SEM) to the end (10.5+/-3.5mg/L SEM) of the study, but this event was not significant. Zinc supplementation intake may cause an increase in serum zinc concentrations, leading to a decrease of inflammation in hemodialysis patients.