In this study, a novel method for the sulfur removal of the mixed fuel (70% vacuum gas oil and 30% natural gas condensate) using ozone microbubbles as the oxidant followed by solvent extraction in a millichannel has been investigated. In this regard, the mixed fuel was saturated with a gaseous oxidant (i.e., ozone) in a pressurized saturation chamber. After that, dissolved ozone appeared in the form of microbubbles by passing through a pressure-reducing valve, which could perform the oxidation of sulfur-containing compounds efficiently. It was revealed that ∼75% sulfur removal was achieved by oxidation of fuel for 60 min with an ozone saturating pressure of 2.5 barg, while the same level of the desulfurization was attained for 90 min of oxidation at 1.5 barg. Afterward, the oxidized sulfur compounds were removed by extraction inside a millichannel. It was found that the sulfur removal efficiency could be enhanced by 12% in comparison with solvent extraction using a batch contactor. Chemical consumption and energy input requirement are the other factors characterized in this study and compared with the conventional oxidative desulfurization process. The results have revealed that applying a saturating pressure of 1.5 barg for 120 min of ozonation has decreased the energy consumption by about 15% to achieve a certain desulfurization level.