The prevalence of chronic fatigue (CF), elevated fatigue levels >six months, is 2.5-3 times higher in long-term Hodgkin disease survivors (HDSs) than in the general population (GP). This is the first study comparing the quality of life (QoL) of chronic fatigued survivors with that of chronic fatigued subjects in the GP. The fatigue questionnaire (FQ) and the SF-36 were mailed to 591 HDSs successfully treated at the Norwegian Radium Hospital from 1971 to 1997. Patient data were compared with nationally representative GP data, adjusted for age, gender and education. The response rate was 80% (N = 475), median follow-up 195 months (range 53-431), mean age 46 years (range 21-74), and 44% were females. HDSs reported significantly poorer QoL than the GP with lower scores on six of eight SF-36 scales (P < 0.001). The subgroup of HDSs with chronic fatigue however (N = 142/475, 30%) had better QoL on five of eight SF-36 scales than subjects with CF in the GP (N = 224/2141, 11%), particularly mental health and emotional role-functioning (P = 0.005 and <0.0001). No differences were found on the physical SF-36 domains. Overall, HDSs reported lower QoL than the GP, in particular the HDSs with CF. Their QoL was similar to that of GP subjects with CF, but with significantly better mental health status. This suggests that CF in long-term survivors may be associated with more physical than psychological aspects of long-term cancer survivorship.