A study is reported on the effects of task load and task motivation on the relationship between effort and fatigue in a demanding life-support simulation, aimed to test the hypothesis that effort, rather than demands, was the direct cause of fatigue in task performance. This was done by independently manipulating two factors that affect effort: task load and task motivation. A total of 28 participants were tested in a mixed 3 × 2 factorial design; task load (within-Ss) was varied in terms of the number of manual control systems (1, 3 or 5) that needed to be managed during a 100 min session, while task motivation (between-Ss) was defined by instructions (standard vs. enhanced) designed to influence the level of voluntary commitment to task goals. Effort and fatigue were measured by self report, as were perceived demands and anxiety (included as manipulation checks). While both task load and task motivation led to an increase in effort, there was a stronger fatigue response to task load under enhanced task motivation. As predicted, while both perceived demands and anxiety increased with task load, they were not affected by task motivation. An independent assessment of after-effects of fatigue on a fault finding task showed an increased use of low effort strategies under enhanced task motivation. The findings support the hypothesized effort → fatigue linkage. During task performance, fatigue is a consequence not of task demands per se, but of the level of commitment of effort in meeting demands.