Long lasting involvement in a cognitive task leads to mental fatigue. Substantial efforts have been undertaken to understand this phenomenon. However, it has been demonstrated that some changes with time on task are not only related to mental fatigue. The present study intends to clarify these effects of time on task unrelated to mental fatigue on response selection processes at the behavioural and electrophysiological level (using event-related potentials, ERPs). Participants had to perform a Simon task for more than 3 hours and rated their experienced mental fatigue and motivation to continue with the task at several time points during the experiment. The results show that at the beginning of the experiment some unspecific modulations of training and adaptation are evident. With time on task participants’ ability to resolve response conflict appears to become impaired. The results reveal that time on task effects cannot be completely explained by mental fatigue. Instead, it seems that an interplay of adaptation at the beginning and motivational effects in the course of a task modulate performance and neurophysiological parameters. In future studies it will be important to account for the relative contribution of adaptation and motivation parameters when time on task effects are investigated.