In many diseases across a range of pathologies (e.g., cardiopulmonary, neuromuscular, and cancer), chronic dyspnea, particularly on exertion, is a major debilitating symptom often associated with clinical anxiety/depression. This study aims to explore the interaction between mood state and exertional dyspnea in a healthy population. Following familiarization, 20 healthy subjects (27-54 years old) performed six 5-min treadmill tests on three separate days. On each day subjects viewed randomly assigned images designed to induce positive, negative, or neutral mood states (International Affective Picture System). For each condition, at minute intervals, subjects rated dyspnea (sensory and affective domains) in the first test and mood (valence and arousal domains) in the second test. Oxygen uptake (V̇o2, liters/min), carbon dioxide production (V̇co2, liters/min), ventilation (V̇e, liters/min), respiratory frequency (fR, beats/min), and heart rate (HR, bpm), were measured throughout the exercise. V̇o2, V̇co2, V̇e, HR, and fR were not statistically significantly different among the three mood states (P > 0.05). Mood valence was significantly higher with parallel viewing of positive (last 2-min mean ± SE = 6.9 ± 0.2) compared with negative pictures (2.4 ± 0.2; P < 0.001). Both sensory and affective domains of dyspnea were significantly higher during negative (sensory: 5.6 ± 0.3; affective: 3.3 ± 0.5) compared with positive mood (sensory: 4.4 ± 0.4, P < 0.001; affective: 2.1 ± 0.4, P = 0.002). These findings suggest that positive mood alleviates both the sensory and affective domains of exertional dyspnea in healthy subjects. Thus the treatment of anxiety/depression in dyspenic populations could be a worthwhile therapeutic strategy in increasing symptom-limited exercise tolerance, thereby contributing to improved quality of life.