The present study aimed to investigate the relationship between the mechanical load during resistance exercise and the elicited physiological responses. Ten resistance-trained healthy male subjects performed 1 set of resistance exercise each at 55%, 70%, and 85% of 1 repetition maximum for as many repetitions as possible and in 4 training modes: 4-1-4-1 (4 s concentric, 1 s isometric, 4 s eccentric, and 1 s isometric successive actions), 2-1-2-1, 1-1-1-1, and explosive (maximum velocity concentric). Mean concentric power and total concentric work were determined. Oxygen uptake (V̇O2) was measured during exercise and for 30 min post exercise. Total volume of consumed oxygen (O2 consumed) and excess post-exercise oxygen consumption (EPOC) were calculated. Maximum blood lactate concentration (LAmax) was also determined. V̇O2 exhibited a linear dependency on mean concentric power. Mean concentric power did not have a detectable effect on EPOC and LAmax. An augmentation of total concentric work resulted in significant linear increase of O2 consumed and EPOC. Total concentric work caused a significant increase in LAmax. In general, a higher mechanical load induced a larger physiological response. An increase in mean concentric power elicited higher aerobic energy turnover rates. However, a higher extent of total concentric work augments total energy cost covered by oxidative and (or) glycolytic pathways.