The objective of the present study was to verify the energy expenditure (EE), energy system contributions and autonomic control during and after an acute low-load or high-load resistance training (RT) protocol to momentary failure (MF) in young adults. Eleven young men (22 ± 3 yrs, 71.8 ± 7.7 kg; 1.75 ± 0.06 m) underwent a randomized crossover design of three knee extension acute protocols: a low-load RT [30% of their maximal strength (1RM); RT30] or a high-load RT (80% of 1RM; RT80) protocol, with all sets being performed to MF; or a control session (Control) without exercise. Participants were measured for EE, energy system contributions, and cardiac autonomic control before, during, and after each exercise session. Exercise EE was significantly higher for RT30 as compared to RT80. Furthermore, post measurements of blood lactate levels and the anaerobic lactic system contribution were significantly greater for RT30 as compared to RT80. In addition, parasympathetic restoration was lower for RT30 as compared to RT80. In conclusion, a low-load (30% 1RM) RT session produced higher EE during exercise than a high-load (80% 1RM) RT session to MF, and may be a good option for fitness professionals, exercise physiologists, and practitioners when choosing the optimal RT protocol that provides more EE, especially for those who want or need to lose weight.