BACKGROUND AND AIMS: Chronic kidney disease is associated with enhanced inflammatory response and autonomic dysfunction. Evidence exists of a potential interaction of inflammation and nervous system. We sought to investigate determinants of heart rate variability (HRV) and relations between the inflammatory markers C-reactive protein (CRP) and interleukin-6 (IL-6) and autonomic tone in patients with moderate and severe chronic kidney disease and in maintenance hemodialysis patients, and relations of CRP and IL-6 with clinical characteristics and lipid levels. METHODS: This was a cross-sectional study of 51 hemodialysis and 53 moderate and severe chronic kidney disease patients. Autonomic tone was assessed using 24-hour HRV analysis in time and frequency domain. All patients underwent measurements of high sensitivity CRP, IL-6 and lipid levels. RESULTS: CRP and IL-6 were elevated in the non-dialysis group at levels similar to hemodialysis patients. Hemodialysis patients had lower total cholesterol, LDL cholesterol and apolipoprotein B levels (p < 0.05), and in this group of patients lipids were related to CRP and IL-6 (p < 0.05). The inflammatory marker IL-6 was associated to HRV in the moderate and severe chronic kidney disease group (R = -0.4, p < 0.01 for standard deviation of RR intervals and very low frequency power, R = -0.5, p < 0.01 for standard deviation of all five-minute RR intervals, R = 0.35, p < 0.05, for total power and low frequency power). Adequacy of dialysis, but not the inflammatory markers, was associated to HRV in the hemodialysis group (R = 0.6, p < 0.01 for high frequency power). CONCLUSION: Enhanced inflammatory response occurs already in stages 3 and 4 chronic kidney disease. IL-6 is related to HRV in these patients, but not in the hemodialysis group, suggesting that IL-6 may interact with autonomic tone in that stage of disease.