Globally, large mammal populations have sharply declined due to multiple stressors, with disease and climate change posing substantial challenges for managing protected species with low abundances. Peninsular bighorn sheep (Ovis canadensis nelsoni) are a distinct, federally endangered population of desert bighorn sheep native to the Peninsular Ranges of Southern California. This population has undergone dramatic fluctuations over the last five decades with disease believed to be a primary driver of decline. However, limited effort has been focused on how climate change will impact the population’s long-term viability given expected increases in drought frequency and intensity in the region. Here, we assessed how this population may respond to future disease and drought conditions by develop+ing an integrated population model in collaboration with government and private agencies to best capture ecological processes for this data-limited species. Our approach evaluated various scenarios projecting how population trends may change over the next 25 years under constant conditions, increased disease or drought frequency and intensity, and their synergistic effects. Our approach provides a flexible framework to evaluate the impacts of interacting stressors, helping guide proactive management strategies for date-poor at-risk endangered species.