Obesity is associated with difficulties due to stigma and loneliness. These impact negatively on individuals’ quality of life and behaviour change efforts. Increased sensitivity to others’ negative feedback might play a role in the maintenance of these difficulties and could be addressed in psychological interventions. We conducted a systematic review of interpersonal difficulties in individuals with obesity, across the lifespan. We investigated early interpersonal adversity (i.e. frequency of teasing/bullying), perceived interpersonal stress and quality of social life, based on a rejection sensitivity model. The databases PubMed, Web of Knowledge and AGRIS, Embase, Medline and PsychINFO were searched for published peer-reviewed journal articles (1980-June 2018). Thirty-two studies met inclusion criteria. Results from the meta-analyses (n = 16 studies) indicated that overweight/obese individuals reported more frequent experiences of teasing/bullying, greater interpersonal stress and poorer quality of social life than healthy weight individuals. Findings in the systematic review aligned to this evidence. Psychological interventions targeting increased sensitivity to negative interpersonal feedback could improve interpersonal functioning and, in turn, eating behaviours in individuals with obesity.