Cocoyam is highly seasonal and perishable. An efficient wholesale marketing system makes its consumption, round the year possible, reduces postharvest losses for greater marketing margin. This study examined the determinants of marketing margin and efficiency of wholesale marketing of cocoyam in Southeast, Nigeria. The specific objectives were to examine the socio-economic characteristics of cocoyam wholesale marketers, estimate the marketing margin and efficiency of the wholesale marketing of cocoyam and examine the socio-economic factors of the wholesalers affecting their net marketing margin. Multistage, purposive and random sampling techniques were used to generate relevant data using a structured questionnaire administered to 216 cocoyam wholesale marketers in 18 markets in three states of the southeast (Anambra, Enugu and Imo). Descriptive statistics and inferential statistics (Gross margin and Efficiency Analysis and Multiple Regression) were used to analyse the data. Result on the socio economic characteristics of cocoyam wholesale marketers shows that no marketer was below the age 20 years and above 60 years with the mean age of 46 years. Majority (80%) of the marketers were married with mean family size of 5. The high gross margin of ₦20,387,212 and net marketing margin of ₦2,817,524 indicates profitability and the efficiency coefficient value of 84% indicates a high level of efficiency. The results of the influence of socio-economic variables of the respondents on the net marketing margin shows that six variables (age, marketers` experience, years of formal education, selling price, purchase price and quantity of cocoyam sold) were statistically significant while the remaining variables were not. The R2 value of 0.875 implied that 88% of variation in the net marketing income realized by the marketers was due to variations in the independent variables and the remaining 12% was as a result of stochastic noise. The F-value of 189.390 was statistically significant at 5% level of probability. This implied that socio-economic variables of the respondents together significantly influenced net marketing income, and that regression model was a good fit. It is recommended that adequate facilities such as good road network be provided especially to the rural areas (production site), storage and processing facilities should be subsidized by government for efficient marketing of agricultural produce, especially cocoyam.