Obesity represents a serious health issue affecting millions of people in Western industrialized countries. The severity of the medical problems it causes is paralleled by the fact that obesity has become a social stigma that affects the psychological health-related quality of life of individuals with weight problems. Our study, with 111 obese patients of a Spanish hospital, focused specifically on how overt and subtle discrimination is related to subjective well-being (affect balance and life satisfaction) and physical health-related quality of life. It was shown that overt (r = –.28, p < .01 with affect balance; r = –.26, p < .01 with life satisfaction) and subtle discrimination (r = –.28, p < .01 with affect balance; r = –.27, p < .01 with life satisfaction) were negatively linked with subjective well-being, and that there was a negative correlation between overt discrimination and physical health-related quality of life (r = –.26, p < .01). Additionally, it was found that overt discrimination was a mediator variable in the relationship between physical health-related quality of life and subjective well-being using the Baron and Kenny procedure. Finally, it is discussed the relationship between discrimination, subjective well-being and physical health-related quality of life in obese people.