The effects of mental fatigue on attention were assessed. Subjects performed a visual attention task for 3 h without rest. Subjective levels of fatigue, performance measures and EEG were recorded. Subjective fatigue ratings, as well as theta and lower-alpha EEG band power increased, suggesting that the 3 h of task performance resulted in an increase in fatigue. Reaction times, misses and false alarms increased with time on task, indicating decreased performance efficiency in fatigued subjects. Subjects were unable to inhibit automatic shifting of attention to irrelevant stimuli, reflected by a larger negativity in the N1 latency range for irrelevant, compared to relevant stimuli. This difference in negativity was unaffected by time on task. However, N1 and N2b amplitude did change with time on task: N1 amplitude decreased, and the difference in N2b amplitude between relevant and irrelevant stimuli (larger N2b amplitude evoked by relevant stimuli) decreased with time on task. The results indicate a dissociation in the effects of mental fatigue on goal-directed (top-down) and stimulus-driven (bottom-up) attention: mental fatigue results in a reduction in goal-directed attention, leaving subjects performing in a more stimulus-driven fashion.