Abstract Objective The aim of the study was to assess the association of body mass index (BMI) and Health-Related Quality of Life (HRQoL), and the relative importance of BMI in explaining variation in QoL among stage I or II endometrial cancer (EC), independent of comorbidities, socio-demographic and clinical characteristics. Methods A population-based, cross-sectional survey was conducted in 2008 among endometrial cancer survivors diagnosed between 1999 and 2007 sampled from the Eindhoven Cancer Registry. The HRQoL (SF-36), EC specific HRQoL (EORTC-QLQ-EN24), comorbidities (SCQ) and fatigue (FAS) questionnaire were completed by 666 endometrioid EC survivors. Multivariate regression analyses were used to assess the associations of HRQoL with BMI reported at time of questionnaire completion and to assess the percentage of variance in HRQoL outcomes explained by BMI (R2), (controlled for socio-demographic and clinical characteristics and comorbidity). Results Of all women, 432 (67.6%) were pre-obese (BMI 25–30) or obese (BMI >30). Increased BMI was associated with decreased physical function, decreased vitality, more lymphoedema symptoms, decreased sexual/vaginal problems, less taste change and more fatigue symptoms. BMI added significantly to the explained variance of physical function (4.3%), physical limitations in daily life (role physical; 0.7%), bodily pain (1.5%), vitality (1.6%), emotional limitations in daily life (role emotional; 0.9%), lymphoedema symptoms (5.2%), sexual/vaginal problems (3.2%), urologic problems (0.7%), and fatigue (1.4%). Conclusion BMI was related to several HRQoL outcomes. Therefore BMI needs to be taken into account in HRQoL studies. Moreover, future research should assess if interventions to decrease BMI in obese EC survivors might improve HRQoL.