In an earlier study, we found that cognitive-behavioral therapy (CBT) delivered by general practitioners (GPs) for fatigue among employees on sick leave was not effective after 12 months. In this study we aim to assess the long-term efficacy of CBT by GPs for fatigue. It was hypothesized that the intervention could prevent deterioration as well as relapse of fatigue complaints and relapse into absenteeism in the long term.Patients who participated in the original randomized controlled trial were followed up 4 years later. Fatigue and absenteeism were the main outcomes.Fatigue and absenteeism were high in the intervention and control groups at the 4-year follow-up. There was no significant difference between the intervention group and the control group on fatigue and absenteeism. The intervention group however tended toward less-favorable outcomes as compared with the control group.Like that of chronic fatigue syndrome, the prognosis of less-advanced fatigue is rather poor. CBT delivered by GPs is not effective in the long term.