In this work, the mercaptan oxidation unit of an oil and gas refinery was simulated and assessed using exergy and parametric sensitivity analysis to identify opportunities for improvement from a technical and energy point of view. The process simulation was performed using Aspen HYSYS V10.1 to obtain extended mass and energy balances. The simulation results were validated with the data available in the literature. The effects of operating conditions on technical performance were analyzed via parametric analysis. The exergy analysis was applied to two case studies: the base case and the resulting case from technical improvements. The global exergy efficiency, irreversibilities, exergy of utilities, and efficiencies per stage were calculated to map process equipment with the highest losses of exergy. A comparison between both base and alternative cases was introduced in order to analyze increments in exergy efficiencies. An exergy efficiency of 84.21% was found for the base case, while for the alternative case after applying parametric sensitivity, it was calculated to be 81.95%. This decrease by 2.26% was attributed to the increase of irreversibilities and exergy of wastes to achieve a product with better quality standards.