This study aimed to identify differences in the acute cardio-respiratory, metabolic and perceptual responses between exercise performed on the treadmill and on the cycle ergometer at several intensities. The sample comprised of 20 voluntary male participants (age = 22.5 +/- 1.8 years; height = 177.7 +/- 7.0 cm; body mass = 72.6 +/- 7.9 kg; fat mass = 7.87 +/- 1.3%) that performed 5 sub-maximal 8 min exercise bouts, interspersed with a 10 min period of passive recovery. Exercise intensity used on the treadmill was 10, 12, 14, 15 and 16 km/h (0% gradient), and 80, 120, 160, 180 and 200 W on the cycle ergometer (65-70 rpm). There was a significant mode effect and also mode x intensity interaction in oxygen uptake and heart rate with higher values in the treadmill protocol (F = 32.0 p = 0.000, eta(2) = 0.65 and F = 132.0 p = 0.000, eta(2) = 0.88, respectively). The respiratory exchange ratio and blood lactate concentrations were not different across modes (F(1, 18) = 1.9 p = 0.183 and F(1, 17) = 0.1 p = 0.964, respectively) and rate of perceived exertion values were higher in the cycle ergometer (F(1, 12) = 1.2 p = 0.288). Generally, results showed a larger exercise mode effect on the cardio-respiratory variables with higher response patterns on the treadmill, differing according to exercise intensity.