During July – September of 2008, 2009, and 2010 endangered age-0 juvenile shortnose suckers were sampled from Upper Klamath Lake, OR in a health evaluation that included the measurement of transforming growth factor – beta (TGF-β) expression in spleen in combination with a histopathology assessment. This analysis was performed to determine if the expression of this immuno-regulator could be used as a component of a larger health evaluation intended to identify potential risk-factors that may help to explain why very few of these fish survive to age-1. Potential associations between TGF-β1 expression, histopathological findings, meristic data as well as temporal and spatial data were evaluated using analysis-of-variance. In this analysis, the absence or presence of opercula deformity and hepatic cell necrosis were identified as significant factors in accounting for the variance in TGF-β1 expression observed in age-0 shortnose suckers (n = 122, squared multiple R = 0.989). Location of sample collection and the absence or presence of anchor worms (Lernaea spp.) were identified as significant cofactors. The actual mechanisms involved with these relationships have yet to be determined. The strength, however, of our findings support the concept of using TGF-β1 expression as part of a broader fish health assessment and suggests the potential for using additional immunologic measures in future studies. Specifically, our results indicate that the measure of TGF-β1 expression in age-0 shortnose sucker health assessments can facilitate the process of identifying disease risks that are associated with the documented lack of recruitment into the adult population.