Background and aim: Metabolic disorders are prevalent in patients with chronic kidney disease (CKD) and may lead to protein energy wasting. Adipokines play a vital role in energy metabolism. We aimed to determine the relationship between adipokine levels and resting energy expenditure (REE) in patients with CKD.Methods: A total of 208 patients in non-dialyzed CKD stages 3–5 were enrolled in this cross-sectional study. Serum adipokines (leptin, adiponectin, and interleukin 6 (IL-6) were measured using enzyme-linked immunosorbent assay. Patient's REE was measured using indirect calorimetry. Fat mass (FM) and lean tissue mass (LTM) were measured using multiple-frequency bioimpedance analysis. Spearman correlation analyses and multivariate linear regression models were used to assess the association between serum adipokines and REE.Results: The mean age was 52.7 ± 14.6 years, and 26.9%, 26.4%, and 46.7% of our participants had CKD stages 3, 4, and 5, respectively. The median values of serum adiponectin, leptin, and IL-6 were 470.4 (range, 291.1–802.2), 238.1 (range, 187.9–418.4), and 4.0 (range, 2.4–9.5) pg/mL, respectively. The male participants had significantly lower FM% (P = 0.001) and lower leptin levels (P < 0.001) than the female participants. After adjusting for age, diabetes, high-sensitivity C-reactive protein, intact parathyroid hormone, LTM, and FM, multiple linear regression analysis revealed that serum leptin levels were significantly positively associated with REE in men rather than in women (P < 0.05). Serum adiponectin levels were inversely associated with REE in men, but this association disappeared while FM was additionally adjusted. Adiponectin levels in women were not correlated with REE (P > 0.05). IL-6 was not significantly associated with REE in either men or women.Conclusions: A sex-specific relationship between serum adipokines (leptin and adiponectin) and REE was observed in patients with CKD stages 3–5, which was partly confounded by FM.Trial registration: This trial was registered at clinicaltrials.gov (NCT03377413).