Midway Atoll in the Northwestern Hawaiian Islands supports the largest breeding colony of Laysan albatross (Phoebastria immutabilis) in the world and is a proposed site for the translocation of endangered Northwestern Hawaiian Island passerine birds such as the Nihoa finch (Telespiza ultima), Nihoa millerbird (Acrocephalus familiaris kingi), or Laysan finch (Telespiza cantans). On the main Hawaiian Islands, introduced mosquito-borne avian malaria (Plasmodium relictum) and avian pox (Avipoxvirus) have contributed to the extinction and decline of native Hawaiian avifauna. The mosquito vector (Culex quinquefasciatus) is present on Sand Island, Midway Atoll, where epizootics of Avipoxvirus have been reported among nestling Laysan albatross, black-footed albatross (Phoebastria nigripes), and red-tailed tropicbirds (Phaethon rubricauda) since 1963. Two introduced passerines, the common canary (Serinus canaria) and the common myna (Acridotheres tristis), are also present on Sand Island and may serve as reservoirs of mosquito-borne pathogens. Assessing disease prevalence and transmission potential at Midway Atoll National Wildlife Refuge (NWR) is a critical first step to translocation of Nihoa endemic passerines. In May 2010 and April 2012 we surveyed Midway Atoll NWR for mosquitoes and evidence of mosquito-borne disease. Although we did not observe active pox infections on albatross nestlings in May 2010, active infections were prevalent on albatross nestlings in April 2012. Presumptive diagnosis of Avipoxvirus was confirmed by PCR amplification of the Avipoxvirus 4b core protein gene from lesions collected from 10 albatross nestlings. Products were sequenced and compared to 4b core protein sequences from 28 Avipoxvirus isolates from the Hawaiian Islands and other parts of the world. Sequences from all Midway isolates were identical and formed a clade with other Avipoxvirus isolates from seabirds that was distinct from other Avipoxvirus isolates from the Hawaiian Islands. Tissue from three presumptive avian pox lesions from common canaries tested negative for Avipoxvirus. Blood samples from 124 canaries and 61 mynas tested negative for Plasmodium by one or more diagnostic tests based on microscopy, serology, or PCR diagnostics. Prevalence of Avipoxvirus infection was highest among albatross nestlings (94.6%) in the vicinity of the septic tanks where adult C. quinquefasciatus reached their highest densities, and data from all sites suggest a positive correlation between mosquito abundance and Avipoxvirus prevalence. Adult C. quinquefasciatus were also locally abundant around fishless, constructed wetlands. Since 1996, infrastructure removal and source reduction efforts by the refuge have greatly reduced the availability of underground and container habitats for larval mosquitoes on Sand Island. However, the creation of artificial wetlands and a central septic system on Sand Island has resulted in new, highly productive larval mosquito habitat for C. quinquefasciatus. Despite the presence of endemic Avipoxvirus in albatross nestlings and the introduction of mosquito vectors and two susceptible passerine species in the last century, we found no evidence of the avian malaria Plasmodium relictum or a passerine-infecting Avipoxvirus on Midway Atoll NWR that would interfere with the successful translocation of endemic Northwestern Hawaiian Island passerines. Without eradication of mosquitoes from Midway Atoll, however, periodic epizootics of Avipoxvirus among nestling seabirds will likely continue, and the introduction of malaria and passerine strains of Avipoxvirus from migratory birds will remain a long-term threat to passerine restoration programs.