Fatigue is often experienced after liver transplantation. The aim of this cross-sectional study was to assess the severity of fatigue in liver transplant recipients. In addition, the nature of fatigue and factors that may be associated with severity of fatigue after liver transplantation were explored. Ninety-six patients up to 15 years after liver transplantation were included. Severity of fatigue and nature of fatigue were assessed with the Fatigue Severity Scale (FSS) and the Multidimensional Fatigue Inventory, respectively. Furthermore, age, gender, indication for transplantation, time since transplantation, immunosuppressive medication, self-experienced disability, and health-related quality of life (HRQoL) were assessed as potential associated factors. Sixty-six percent of all patients was fatigued (FSS > or = 4.0) and 44% of all patients was severely fatigued (FSS > or = 5.1). Patients experienced physical fatigue and had reduced activity rather than mental fatigue and reduced motivation. Age, gender, self-experienced disabilities, and HRQoL were correlated with severity of fatigue. Results of the study indicate that fatigue is a major problem in patients after liver transplantation and no indications were found that complaints of fatigue improve over time. Liver transplant recipients experience physical fatigue and reduced activity rather than mental fatigue and reduced motivation. These findings have implications for the development of interventions needed to rehabilitate persons after liver transplantation.