Background: The higher order processes involved in self-regulation are generally thought to depend on cognitive (attentional/executive) functions with limited resources. Experimental studies further show that exerting self-control in a first task results in decreased performance in other following self-control tasks, which may be interpreted as the consequence of either effective or perceived resource depletion outlasting the first task. Given that higher order cognitive/attentional processes are also considered to be involved in pain modulatory mechanisms, we tested the idea that pain could be influenced by prior mobilization of cognitive resources. Methods: The present study investigated the consequences of performing a cognitively demanding task on subsequent pain (ratings) and spinal nociceptive responses (nociceptive flexion reflex, NFR) elicited by noxious electrical stimulations in healthy volunteers. Participants received four noxious stimulations immediately after each of six successive blocks (2 min each) of a numerical Stroop task in a neutral condition (low cognitive demand) and six successive blocks in an interference condition (high cognitive demand). Results: Results revealed that pain was rated higher following the condition requiring higher cognitive control. A similar effect was observed on the NFR. Conclusions: These findings suggest that pain regulation mechanisms including the descending pain modulatory system may be less efficient after the performance of tasks requiring high cognitive control resulting in stronger pain experience.