Recently, exergy analysis has attracted great attention of the scientific community as an attractive tool for evaluating energetic efficiency of any process. In this work, the simulation of the amine treatment unit in a Latin-American refinery was performed in order to apply the exergy analysis tool to identify alternatives of improvement. The industrial amine treatment unit was simulated using Aspen plus software, which provided extended energy and mass balances. To calculate irreversibilities of the process and global exergy efficiencies per stages, the general methodological procedure of exergy analysis was used. To this end, physical and chemical exergies were found for compounds involved within the process. The values estimated for total irreversibilities, exergy of utilities, and exergy of wastes in the treatment of the sulfur-rich amine allowed us to analyze the stages that require reductions in waste generation and utility consumption. For a processing capacity of 72.08 t/h of rich amine, results revealed that the overall exergy efficiency was 83.81% and the total irreversibility was 1.69 × 105 MJ/h, where 23.6% corresponds to the total exergy by residues (3.98 × 104 MJ/h). The novel strategy to use exergy analysis for process optimization proved to be useful to detect critical stages and prioritize actions to improve.