Data gathered by wildlife laboratories from submissions provides a rare opportunity to examine long-term, demographic, temporal and spatial patterns of mortality, which may have important management implications. From 1976-2012, we retrospectively examined records of avian case submissions to the Southeastern Cooperative Wildlife Disease Study (SCWDS; University of Georgia, USA) in order to determine the relative importance of mortality factors for birds over time. During this period, SCWDS received 2,583 wild bird specimens from the orders Apodiformes, Caprimulgiformes, Cuculiformes, Passeriformes, and Piciformes originating from 22 states, mostly located in the southeastern USA. Data from 2,001 of these birds were analyzed using log-linear models to explore correlations between causes of mortality, taxonomic family, demography, geographic location, and seasonality. Toxicosis was the most frequent cause of mortality, followed by trauma, bacterial infection, physiologic stress, and viral infections. Birds submitted during fall and winter had a higher prevalence of parasitic infections, trauma, and toxicoses, while those submitted during the spring and summer were more likely to die of infectious disease, physiological stress, or trauma. We noted a decrease in toxicoses concomitant with an increase in bacterial infections and trauma diagnoses after the mid-1990s. The majority of adults died from toxicoses, whereas the main cause of death in juveniles was physiologic stress, trauma and viral infections. Infectious agents were frequently diagnosed within the Cardinalidae and Fringilidae families, while non-infectious etiologies were the primary diagnoses within the families Bombycillidae, Parulidae, Sturnidae, Turdidae, and Icteridae. It is important to note that there are inherent limitations in the interpretation of data from diagnostic laboratories, as submission of cases varies in timing, frequency, location and species, and is often influenced by factors such as media coverage of high-profile events.