We conducted benefit-cost analysis of outbreak and surveillance costs for HPAI H5N1in poultry in Nigeria. Poultry's death directly cost US$ 939,734.0 due to outbreaks. The integrated disease surveillance and response originally created for comprehensive surveillance and laboratory investigation of human diseases was adapted for HPAI H5N1 in poultry. Input data were obtained from the field, government documents and repositories and peer-reviewed publications. Actual/forecasted bird numbers lost were integrated into a financial model and estimates of losses were calculated. Costs of surveillance as alternative intervention were determined based on previous outbreak control costs and outputs were generated in SurvCost® with sensitivity analyses for different scenarios.Uncontrolled outbreaks will lead to loss of over US$ 2.2 billion annually in Nigeria with 47.8% of the losses coming from eggs. The annual cost of all animal related health activities was <US$ 99.0 million, only one-third of this amount was linked with H5N1 surveillance and response activities. Recurrent cost was 96.2% of the total surveillance and response costs, and 31.0% of the HPAI surveillance cost was spent on personnel with 3.8% as capital cost. Cost-wisely, routine monitoring and surveillance for HPAI are 68 times more cost effective than to do nothing. Assuming that successful control and eradication of HPAI H5N1 is partially attributable to H5N1 surveillance and response, a quarter or half of the success will result in 17 or 34 times more benefits. Although animal surveillance and response activities for avian influenza appeared expensive, their implementation are economically cost beneficial for developing countries.