This paper documents a mass en route mortality event of adult summer chum salmon (Oncorhynchus keta) returning to the Koyukuk River, Alaska in the Yukon River watershed. In response to reports from local communities, researchers (including the author) surveyed ca. 315 km of river on July 26 and 27, 2019 and counted 1,364 dead individuals, but this likely reflects a small fraction of the true number of fish that died. We sampled 73 carcasses to confirm death occurred prematurely prior to complete maturation and spawning, to quantify sex and length. Visual inspection revealed a substantial fraction exhibited patterns of fungal growth consistent with secondary infections of skin lesions caused by the ubiquitous natural bacterial pathogen Flavobacterium columnare. Water temperatures during the survey averaged 17.1°C and the water was approximately 85% saturated with oxygen (ca. 8.5 mg/L), which likely contributed to the stress for upstream migrants. Evidence suggests size-selective en route mortality as female migrants that died were 2% and male migrants 5% shorter than individuals that survived to their spawning grounds on Henshaw Creek. This translates to very strong estimates of natural selection using standardized selection differentials, though randomization tests of size data revealed this observed outcome of selection was expected to occur 25% of the time due to chance alone. It is unclear whether selection acts on body size directly or indirectly through correlated phenotypic traits such as run timing. The mortality event likely underpins the below average returns of summer chum salmon to the Koyukuk in 2019, suggesting an impact on spawner abundance. The future consequences of this, or potentially increasingly frequent, en route mortality events for population productivity and the extent to which genetic adaptation or adaptive phenotypic plasticity of migration behavior may facilitate persistence of these populations is unknown.