A cohort study was conducted in the livestock-wildlife interface areas of Zambia to determine cattle mortality and commercial off-take rates among adult cattle as well as factors influencing them. A total of 416 animals from 43 herds were followed up for one year and animals were individually identified and their fate was indicated as sold, slaughtered, dead or present as appropriate. The overall mortality incidence risk was estimated at 7.5%. Cattle in Kazungula were at a greater risk of dying compared to those in Blue Lagoon and Lochnivar. Annual off-take was estimated at 13.7% (8.1-19.3%), unadjusted values, and 16.4% (8.1-24.5%) after adjusting for sampling fraction in primary sampling units (herds) and area stratification. Area variations were observed with Kazungula recording the highest in both instances, which was attributed to a contagious bovine pleural pneumonia (CBPP) outbreak. Herd size and gender were observed to influence cattle mortality rates. Cattle in the middle-sized herds (50-150 cattle) recorded high mortality rates (OR = 3.91) compared to smaller herds (10-50) and so were females compared to males (OR = 4.16). The logistic regression model showed that cattle death was influenced by managerial factors and that off-take rates tend to increase in the face of disease outbreaks.