Skeletal muscle fatigue and exercise performance are novel areas of research and clinical application in the photobiomodulation field, and positive outcomes have been reported in several studies; however, the optimal measures have not been fully established.Context: To assess the acute effect of photobiomodulation therapy (PBMT) combining superpulsed lasers (low-level laser therapy) and light-emitting diodes (LEDs) on muscle performance during a progressive cardiopulmonary treadmill exercise test.Objective: Crossover study.Design: Laboratory.Setting: Twenty untrained male volunteers (age = 26.0 ± 6.0 years, height = 175.0 ± 10.0 cm, mass = 74.8 ± 10.9 kg).Patients or Other Participants: Participants received PBMT with either combined superpulsed lasers and LED (active PBMT) or placebo at session 1 and the other treatment at session 2. All participants completed a cardiopulmonary test on a treadmill after each treatment. For active PBMT, we performed the irradiation at 17 sites on each lower limb (9 on the quadriceps, 6 on the hamstrings, and 2 on the gastrocnemius muscles), using a cluster with 12 diodes (four 905-nm superpulsed laser diodes with an average power of 0.3125 mW, peak power of 12.5 W for each diode, and frequency of 250 Hz; four 875-nm infrared LED diodes with an average power of 17.5 mW; and four 640-nm red LED diodes with an average power of 15 mW) and delivering a dose of 30 J per site.Intervention(s): Distance covered, time until exhaustion, pulmonary ventilation, and dyspnea score.Main Outcome Measure(s): The distance covered (1.96 ± 0.30 versus 1.84 ± 0.40 km, t19 = 2.119, P < .001) and time until exhaustion on the cardiopulmonary test (780.2 ± 91.0 versus 742.1 ± 94.0 seconds, t19 = 3.028, P < .001) was greater after active PBMT than after placebo. Pulmonary ventilation was greater (76.4 ± 21.9 versus 74.3 ± 19.8 L/min, t19 = 0.180, P = .004) and the score for dyspnea was lower (3.0 [interquartile range = 0.5–9.0] versus 4.0 [0.0–9.0], U = 184.000, P < .001) after active PBMT than after placebo.Results: The combination of lasers and LEDs increased the time, distance, and pulmonary ventilation and decreased the score of dyspnea during a cardiopulmonary test.Conclusions: