Purpose: This study investigated the physiological effects of wearing a mouthguard during submaximal treadmill exercise. Method: Twenty-four recreationally active males (M[subscript age] = 21.3 ± 2.4 years, M[subscript height] = 1.78 ± 0.06 m, M[subscript weight] = 81.9 ± 10.6 kg, M[subscript body mass index] = 25.8 ± 3.4 kg·m[superscript -2]) performed incremental, continuous exercise at 2, 4, 6, and 8 mph (3.2, 6.4, 9.7, 12.9 kph) for 5 min at each speed on a motor-driven treadmill on 2 separate occasions in a randomized, crossover, counterbalanced design while wearing or not wearing a self-adaptable "boil and bite" mouthguard. Respiratory rate (RR), tidal volume (V[subscript T]), ventilation (V[subscript E]), oxygen consumption (VO[subscript 2]), respiratory exchange ratio (RER), and heart rate (HR) data were averaged during the last 60 s of each exercise stage; blood lactate (LA) was measured before exercise and 3 min and 10 min following exercise. Results: Repeated-measures analysis of variance revealed that mouthguard use failed to alter the response of RR, V[subscript T], V[subscript E], VO[subscript 2], RER, and HR to treadmill exercise (p > 0.05), although each variable did increase in magnitude as a result of increasing treadmill speed (p < 0.001). Although increasing to above resting values at both 3 min and 10 min (p < 0.001) after cessation of exercise, LA levels also displayed no differences with mouthguard use (p > 0.05). Conclusion: Despite predictable increases in respiratory, metabolic, and cardiovascular variables in response to incremental exercise, the presence of a mouthguard failed to affect the magnitude or nature of these physiological responses.