Purpose Zinc plays a vital role in the body, including inflammation and oxidative stress mitigation, which are common com plications in patients with chronic kidney disease (CKD) undergoing hemodialysis (HD). This cross-sectional observational study evaluated the correlation between zinc status and inflammatory markers in patients undergoing HD. Methods Twenty patients (ten men, 50 (14.5) years, and BMI of 26.7 (6.8) kg/m2) were evaluated. Plasma and erythrocyte zinc levels were measured by inductively coupled plasma mass spectrometry (ICP-MS). Nrf2 and NF-kB mRNA expressions were assessed in PBMCs using quantitative real-time polymerase chain reaction (RT-qPCR), and malondialdehyde (MDA) plasma level was used as a lipid peroxidation marker. Routine biochemical parameters, including C-reactive protein (CRP) levels, were assessed by commercial BioClin® kits. Results As expected, we observed a tendency to have an inverse correlation between erythrocyte and plasma zinc (Zn) levels (rho = − 0.41, p = 0.06). The CRP plasma levels were negatively associated with Zn plasma levels (rho = − 0.53, P = 0.01) after age, time on dialysis, sex, and BMI adjustment. Conclusion A negative correlation was observed between plasma Zn levels and a marker of inflammation (CRP), suggesting a possible role of Zn in the inflammation status of these patients. Trial registration ClinicalTrials.gov Identifier: NCT04600258.