This study on the determinants of profitability among smallholder cattle farmers under Animal African Trypanosomosis (AAT) infestation in Edo State, Nigeria examined the socioeconomic characteristics of smallholder cattle farmers and establish the determinants of profitability in cattle farming business. A multi stage and snowball sampling techniques were adopted in selecting a total of 270 pastoralists from 27 communities in 9 Local Government Areas across the three agricultural zones of the State. Data was obtained through the use of structured questionnaire and analyzed using descriptive statistics and multiple regression analysis. Results showed that all the pastoralists sampled were males (100%), and the modal age of respondents was between 26 and 30 years (39.9%). The mean farming experience was 15 years and 62.3% had some level of education with the mean years of schooling of 6.0 years. The regression result showed that herd size (β 500.60), depreciated total fixed cost (β 5.65), treatment cost (β -10.34), feed cost (β- 2.22), transport cost (β-10.89) and marketing cost (β -10.93) were significant socioeconomic variables that affected revenue of pastoralists in the study area. It was recommended that pastoralists should form cooperative society to pull resources and meet the financial requirements for cattle breeding.