Introduction: Excessive relative interdialytic weight gain (RIDWG, %) is an important risk factor for long-term adverse cardiovascular outcomes in chronic hemodialysis (HD) patients. On the other hand, it may also be an index of good appetite and nutritional status. We aimed to assess the relationship between RIDWG and appetite, nutrition, inflammation parameters of chronic HD patients. Methods: 100 chronic anuric HD patients were enrolled in this prospective study between January 2013 and January 2014. Patients with hospitalization, major surgery, obvious infectious/inflammatory disease, end-stage liver disease, malignancies, and malabsorption syndromes were excluded. Patients were divided into 3 groups according to their RIDWG levels; group 1 = RIDWG < 3%, group 2 = RIDWG: 3-5%, and group 3 = RIDWG > 5%. Results: Group 3 patients were younger (p = 0.011) and had a lower body mass index (BMI) (p = 0.014). Nutrition and inflammation parameters including malnutrition inflammation score (MIS), serum albumin, prealbumin, triceps skinfold thickness, hs-CRP, and TNF-alpha were not significantly different between the groups. Leptin and leptin/BMI ratio were significantly lower in group 3 (p = 0.001). RIDWG was negatively correlated with age (p = 0.001, r = -0.371), BMI (p = 0.001, r = -0.372), leptin (p = 0.001, r = -0.369), leptin/BMI (p = 0.001, r = -0.369). After adjustment for BMI in linear regression analysis, leptin/BMI remained significantly correlated with RIDWG (p = 0.024). Conclusion: This study revealed that RIDWG was associated with younger age, lower BMI and dry weight, and lower serum leptin levels. More detailed studies are needed to validate and dissect the mechanisms of these findings.