Abstract Stress is a contributing factor to painful temporomandibular disorders (TMD). Nevertheless, the underpinnings of this relationship are not fully understood. Objective To investigate the effects of acute mental stress on conditioned pain modulation (CPM) in TMD patients compared with healthy individuals. Methodology Twenty women with chronic myofascial TMD diagnosed according to the RDC/TMD and 20 age-matched healthy women had the CPM assessed before and after a stressful task using the Paced Auditory Serial Addition Task (PASAT) in a single session. Subjective stress response was assessed with the aid of visual analog scale (VAS). Pressure pain threshold (PPT) on masseter muscle was the test stimulus (TS) and immersion of the participant's hand on hot water was the conditioning stimulus (CS) - CPM-sequential paradigm. Results Healthy individuals reported PASAT are more stressful when compared with TMD patients and the stress task did not affect the CPM in neither group. Nonetheless, a negative correlation was observed between change in CPM and change in TS from baseline to post-stress session, which indicates that the greater the increase in PPT after the stress task, the greater was the decrease in CPM magnitude. The correlation was strong for healthy controls (r=- 0.72, p<0.001) and moderate for TMD patients (r=- 0.44, p=0.047). Conclusions The correlation between the change in CPM and the TS change following the stress task may possibly indicate an overlapping pathway between stress-induced analgesia/hyperalgesia and descending pain inhibition.