Background: High indoxyl sulfate (IS) levels and low high-density lipoprotein cholesterol (HDL-c) levels are both risk factors of cardiovascular diseases (CVD) in chronic kidney disease (CKD) patients, the connection between which has not been clearly clarified. This study aimed to explore the relationship between IS and HDL-c levels in early stages of CKD population. Methods: Patients of CKD stage 1-3 were enrolled in this cross-sectional study. Correlations between HDL-c and IS were investigated among various clinicopathological variables.Results: A total of 205 CKD patients (96 men) with a mean age of 43.3 years old were included in this research. There were 96 patients (46 men) in CKD stage1 and 109 (50 men) in CKD stage 2 or stage 3. IS levels were significantly higher in CKD 2+3 group (1.50±1.74μg/ml vs 0.94±0.66μg/ml, p=0.007), while HCL-c levels were lower (1.19±0.39mmol/L vs 1.33±0.45 mmol/L, p=0.017) compared to CKD 1 group. Among all the patients, a negative correlation was observed between IS and HDL-c levels (r=-0.244, p=0.001). IS level was an independent risk factor for low HDL-c (<1.04mmol/L) incidence even after controlling for potential confounders (OR=1.63, 95% CI: 1.11-2.39, p=0.013). IS and HDL-c were both risk factors for predicting CKD stage 3. Conclusions: Metabolic disorder of HDL-c occurs in early CKD stages, probably attributed by increased IS level. Early management of dyslipidemia and uremic toxin retention is important for delaying disease progression and preventing cardiovascular events. Keywords: Indoxyl sulfate, High-density lipoprotein cholesterol, Chronic kidney disease, Cardiovascular disease, Lipids