The purpose of this study was to examine the cardiorespiratory (CR) and stress hormone responses to a combined physical and mental stress. Eight participants (VO2(max) = 41.24 +/- 6.20 ml kg(-1) min(-1)) completed two experimental conditions, a treatment condition including a 37 min ride at 60% of VO2(max) with participants responding to a computerized mental challenge dual stress condition (DSC) and a control condition of the same duration and intensity without the mental challenge exercise alone condition (EAC). Significant interactions across time were found for CR responses, with heart rate, ventilation, and respiration rate demonstrating higher increases in the DSC. Additionally, norepinephrine was significantly greater in the DSC at the end of the combined challenge. Furthermore, cortisol area-under-the-curve (AUC) was also significantly elevated during the DSC. These results demonstrate that a mental challenge during exercise can exacerbate the stress response, including the release of hormones that have been linked to negative health consequences (cardiovascular, metabolic, autoimmune illnesses).