Purpose: To evaluate the association between obesity phenotypes and health-related quality of life (HRQoL) in non-dialysis-dependent CKD patients. Methods: Data from the national CKD-REIN cohort which included 3033 patients with stage 3-4 CKD were used. Patients were divided into three groups: non-obese (NO) patients (BMI < 30 kg/m2), metabolically healthy obese (MHO) (BMI ≥ 30 kg/m2 and ≤ 1 criterion NCEP/ATP III), and metabolically unhealthy obese (MUO) (BMI ≥ 30 kg/m2 and ≥ 2 criteria NCEP/ATP III). HRQoL was measured by the KDQOL-36™ which comprised three disease-specific dimensions: symptoms, effects, and burden and two summaries scores: physical (PCS) and mental (MCS). We used a mixed effect model with adjustment on sociodemographic characteristics and comorbidities. Results: A total of 2693 patients completed the self-administered questionnaires. MHO patients accounted for 3.4% of the cohort and for 12% of obese patients. In the NO group, average HRQoL scores were 77.2 ± 15.9 for symptoms, 83.5 ± 16.5 for effects, 76.8 ± 22.7 for burden, 43.5 ± 9.7 for PCS, and 47.9 ± 7.0 for MCS. In the multivariate analysis, scores were similar in MHO and NO patients, but significantly different with those in MUO patients: symptoms (- 0.7; p = 0.71 vs. - 3.0; p = 0.0025), effects (+ 1.2; p = 0.57 vs. - 4.3; p < 0.0001), burden (+ 2.7; p = 0.31 vs. - 3.6; p = 0.0031), and PCS (- 0.6; p = 0.58 vs. - 4.3; p < 0.0001). MCS was not associated with obesity phenotypes. Conclusions: This study demonstrated an association between obesity phenotypes and QoL in non-dialysis-dependent CKD patients. MUO patients had worse QoL than NO and MHO patients even after adjustment on comorbidities.