Reducing the huge economic losses due to diseases in poultry as the second largest industry in Nigeria after oil means improving the protein intake of the majority. Similarly, this will also promotes a steady income for the teeming farmers. This study investigated the incidence of the lethal avian influenza in Adamawa State, Nigeria, with particular emphasis on the socio-economic and cultural activities of the poultry farmers, economic losses and the possible role of wild birds in the transmission of the disease. Data were collected from 316 and 458 direct and indirect respondents, respectively, from 6 affected villages and a town in 2 Local Government Areas (LGAs): Girei and Yola-North. Results revealed that a larger (25.71%) proportion of the respondents fell within the age range of 31-40 years, with majority (54.91%) as females. While the bulk (54.65%) of the respondents were illiterates, 95.47% of the direct respondents derived their incomes from crop production, whereas 59.17% of the indirect respondents from livestock rearing. About 26,049 birds worth N13, 454,800.00 was cumulative economic loss incurred by the poultry farmers, whereas that of the government was put at N1, 119,781.10. Of the mortalities experienced in the wildlife before the outbreak of the disease, Bubulcus ibis (64.29) and Tadarida nigeriae (86.36) were the highest. The study recommends a massive rural extension on Poultry Production with absolute biosecurity, involving all stakeholders (Veterinary Surgeons, Animal Scientists/health workers, wildlife specialists, Agricultural Economists, Information Officers etc.) in a collaborative form for high synergistic effects.