Broilers are fast-growing birds and serve as a means of white meat highly rich in protein with low cholesterol compared with other livestock. Despite this, there is a dearth of information on its profitability in Nigeria. This study, therefore, investigated the profitability of commercial broiler production enterprise and its determinants in Osun state Nigeria. Data were collected from 200 commercial broiler farmers under the Poultry Association of Nigeria and analysed using descriptive statistics, gross margin and multiple regression. The results revealed that the broiler production enterprise had a gross margin of ₦692,961.83 (USD 1,680.15), a net income of ₦568,036.14 (USD 1,377.26), a benefit-cost ratio of 2.53, an operating cost of 0.26 and 1.53 return on capital invested. These show that the broiler production enterprise was profitable. Cost of feed and disease outbreaks were factors that inhibit the profitability of broiler production venture while years of broiler farming experience, flock size, annual income, access to agricultural extension and access to credit were enhancing factors for the profitability of broiler production enterprise. The extremely severe constraints faced in broiler production were disease outbreaks, inadequate capital and the high cost of feeds. These findings call for government and policy intervention to enhance broiler production profitability. This could be achieved through subsidising the cost of feed, provision of vaccines and drugs to prevent and control disease outbreaks and provision of financial support in the form of credit.