The life cycle of diadromous fishes such as salmonids involves natural mortality in a series of distinct life history stages, occurring sequentially in different habitats. Decades of research have emphasized mortality at the embryo, juvenile, and sub-adult stages but it is increasingly clear that some adults that survive and return to freshwater habitats die during the final homeward migration or after they reach the spawning grounds, prior to breeding. These are termed “en route” and “prespawning” mortality, respectively, and can threaten populations depleted by mortality at previous stages. In this study, we present evidence that the sockeye salmon, Oncorhynchus nerka, population that returns to the Lake Washington Basin, in Washington State, USA, is experiencing both forms of adult mortality. Counts of the salmon entering the basin on their return migration in June and July were compared to counts in the major spawning grounds in September through November for 1995–2018. The disparity has increased markedly in recent years. The counts on the spawning grounds have decreased as a proportion of the number entering the system with an average 49 % of sockeye unaccounted for, consistent with increased en route mortality. In addition, prespawning mortality rates have increased in salmon that reach the Cedar River, the main spawning tributary, both at a hatchery holding adult fish in 1995–2018, and in the naturally spawning populations when monitored in the last five years. Hatchery records indicated <10 % prespawning mortality for 1995–2010, increasing to an average 43 % for 2014 – 2018. Recent carcass surveys in the Cedar River documented that 33.6% (2014), 22.3% (2015), 30.3% (2016) and 50.0% (2018) of female sockeye died before completing spawning. These recent increases in prespawning mortality have been associated with warm water during entry to freshwater, but comparably warm water in past decades had no such effect. Steady warming of river temperatures around the median run completion date from < 8.0 °C to > 13.0 °C was correlated with increased prespawning mortality rates at the hatchery from 1995–2018. We conclude that warming conditions during migration and spawning, in concert with other factors such as infections with pathogens, are responsible for the increased prespawning mortality of adult sockeye salmon that are high enough to threaten the population’s viability.