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We conducted a policy situation analysis in three Mekong region countries, focused on how the animal and human health systems interact to control avian influenza (AI). The study used scoping literature reviews aimed at establishing existing knowledge concerning the regulatory context. We then conducted a series of key informant interviews with national and sub-national government officials and representatives of producers and poultry farmers to understand their realities in managing the complex interface of the two sectors to control AI. We found signs of formal progress in establishing the policy and legislative frameworks needed to enable cooperation of the two sectors but a series of constraints that impede their effective operation. These included the competitive relationships involved, especially with budgetary allocations and mandates that can conflict with each other. Many local actors also view development partners (e.g., bilateral and multilateral donors) as having a dominant role in establishing these collaborations, limiting the extent to which there is local ownership of the agenda. The animal and human health sectors are not equally resourced, with the animal health sector disadvantaged in terms of surveillance and laboratory systems, human resources and financial allocations. Contrasting strategies for achieving objectives have also characterised the two sectors in recent decades, seeing a major shift towards the use of incentive-based approaches in the human health sector but very little parallel development in the animal health sector, largely dependent on command and control approaches. Successful future collaborations between the two sectors are likely to depend on better resourcing in the animal health sector, increasing local ownership of the agenda, and ensuring that both sectors can use the full range of regulatory strategies available to achieve objectives., Highlights • One health is impeded by low-level trust between animal and human health sectors. • Bureaucratic red tape makes information sharing difficult between the two sectors. • Both sectors are establishing legislative and policy frameworks zoonotic outbreaks • Animal health is less resourced for service delivery, surveillance, etc. • Human health sector incentivizes the market, animal health uses command and control.