Focusing of attention is influenced by external features such as the presence of global or local target stimuli, but also by motivation and mood states. In the current study, we examined whether working on cognitively demanding tasks for 2 h, which induces mental fatigue, subsequently had a differential effect on global and local processing. The results showed that, compared to non-fatigued participants, fatigued participants particularly displayed compromised local processing. This indicates that mental fatigue may also manifest itself as effects on attentional focusing. The findings of this study are in line with recent ideas about the nature of fatigue-related cognitive deficits, implying disturbances in the control over attention and behaviour.