Anthropogenic eutrophication contributes to harmful blooms of cyanobacteria in freshwater ecosystems worldwide. In Upper Klamath Lake, Oregon, massive blooms of Aphanizomenon flos-aquae and smaller blooms of other cyanobacteria are associated with cyanotoxins, hypoxia, high pH, high concentrations of ammonia, and potentially hypercapnia. Recovery of the endangered Lost River sucker Deltistes luxatus and shortnose sucker Chasmistes brevirostris in Upper Klamath Lake is obstructed by low survival in the juvenile life stage. Water quality associated with the harmful algal blooms and their decomposition (crashes) is often singled out as the primary cause of juvenile sucker mortality. We investigated this general hypothesis with a review of relevant literature and data from decades of monitoring in Upper Klamath Lake. Microcystins, hepatotoxins produced by some cyanobacteria, are unlikely to be directly lethal to suckers; potential effects of other cyanotoxins that are present in the lake warrant investigation. Dissolved-oxygen saturation declined following bloom crashes, but was infrequently low enough for long enough in Upper Klamath Lake to cause direct sucker mortality. Hypercapnia could potentially reach lethal concentrations in the fall and winter, but did not appear to be associated with the summer algal blooms. pH was highest during peaks in cyanobacteria growth, but infrequently reached directly lethal levels (> 10.3). However, pH frequently reached an observed sub-lethal effect level for juvenile suckers (10.0). Un-ionized ammonia rarely exceeded even the lowest effect level measured for suckers. Rather than act as a direct cause of large-scale mortality, the available evidence suggests that water quality associated with massive blooms of cyanobacteria in Upper Klamath Lake contributes to chronic stress for juvenile suckers and may increase mortality due to other factors.