In patients with very severe closed head injury (CHI), returning to work is often problematic. The present study focuses on a persistent complaint of these patients, viz. mental fatigue. To study this, the effect of sustained workload is assessed in a continuous dynamic divided attention task. Three types of measures are employed: performance loss with time-on-task, and subjective reports and cardiovascular measures of mental effort and distress. Eight very severe CHI patients (mean post-traumatic amnesia duration 51 days, mean age 23 years, (SD 6.4) and eight hospital controls (mean age 29 years, (SD 5.9) were tested. No differences were found between the patients and controls in the effects of task load on performance and the amount of mental effort, even in very demanding simulated work conditions. This parallels previous findings in less demanding laboratory tasks of sustained attention. Effects of CHI were found on both subjective and physiological indicators of distress. Compared to the controls, patients showed stronger effects on systolic blood pressure and subjectively experienced load.