Based on primary data collected from 191 holdings that cultivated the rotation model of 2 rice crops - and 1 sesame crop in 2022 in the Mekong Delta, the economic efficiency of sesame has been estimated by the Cobb - Douglas marginal profit in this study. The estimated results show that the average economic efficiency of holdings is 72,6%; the level of economic efficiency is also likely to increase by 27,4% if the technical efficiency and allocative efficiency of holdings are optimally improved. The level of economic efficiency between holdings has significant differences due to the ability to use inputs in the production process, the distance at the technical level, and the ability to coordinate inputs with prices of input and output factors in the production of holdings. Besides, the results from this study also show that the age, level of education, experience in agricultural production head along with the number of times attending technical training courses, non-agricultural income and number of family workers are factors affecting the economic efficiency of sesame holdings surveyed in the Mekong Delta