A maximal dose of bupropion has enabled subjects to maintain a higher power output than reported during the placebo session in the heat. Because this drug is taken in different doses it is important to know if there is a dose–response relationship with regard to exercise at high ambient temperature. Ten well-trained male cyclists ingested placebo (pla; 200 mg) or bupropion (50%, 75%, 100% of maximal dose: bup50: 150 mg; bup75: 225 mg; bup100: 300 mg) the evening before and morning of the experimental trial. Trials were conducted in 30 °C (humidity 48%). Subjects cycled for 60 min at 55% W max, immediately followed by a time trial to measure performance. Bup100 improved performance (pla: 33'42” ± 2'06”; bup100: 32'06” ± 1'54”; P = 0.035). Bupropion increased core temperature at the end of exercise, while heart rate was higher only in the bup100 trial (P < 0.05). No changes in rating of perceived exertion (RPE) or thermal sensation were found. Lower doses of bupropion were not ergogenic, indicating there was no dose–response effect. Interestingly, despite an increase in core temperature and improved performance in the maximal dose, there was no change in RPE and thermal sensation, suggesting an altered motivation or drive to continue exercise.