Catfish marketing plays a significant role in Nigeria's economy in terms of GDP and job creation, though its potential has not been fully exploited. This investigation assessed the determinants of profitability of fresh catfish marketing in the Uvwie Local Government Area of Delta State, Nigeria. The study focused on profitability (costs and returns), variables affecting profitability, and marketing efficiency of catfish marketing in the study area as its specific objectives. A two-stage sampling technique was employed in selecting the sample size for the study. In Stage 1, three towns in the Uvwie Local Government Area of Delta state were selected. Stage 2 involved the simple random selection of 25% of each of the active registered fresh catfish marketers from the three towns selected. There were eighty-three (83) marketers from Ekpan, 46 from Effurun, and 42 from Ugboroke, which gave a sample size of 171. A well-structured questionnaire was used in order to obtain data from the marketers. This data was analyzed using the multiple linear regression model, budgetary models, and marketing efficiency model. Budgetary model results revealed that the average total revenue (TR) obtained was ₦74,484.44/45.3 per day, net income ₦5,800, gross margin ₦14,279.8, and ROI 0.084. Regression outcome on variables affecting the profitability of fresh catfish marketing noted that age was negatively significant at 5%, and educational level, marketing experience, selling price and sales volume were found to be positively significant at 5%, 10%, 1%, 1% and 1%, respectively, while household size was not significant. Based on the results of the analysis, it was recommended that marketers should organize themselves to form a cooperative society in order to gain easy access to nongovernmental and governmental credit facilities. The government should make provisions for a catfish marketing budget to attract unemployed youths. The study also recommends that the factors that significantly affected the profitability of catfish marketing should not be left out in policy formulation.