BACKGROUND: Effective use of Danio rerio as a preclinical model requires standardization of macronutrient sources to achieve scientific reproducibility across studies and labs. Our objective was to evaluate single cell protein (SCP) for production of open-source standardized diets with defined heath characteristics for the zebrafish research community. We completed a 16-week feeding trial using juvenile D. rerio 31 days post-fertilization (dpf) (10 tanks per diet, 14 D. rerio per tank) with formulated diets containing either a typical fish protein ingredient or a novel bacterial SCP source. At the end of the feeding trial, growth metrics, body composition, reproductive success, and bulk transcriptomics of the liver (RNAseq on female D. rerio only with confirmatory rtPCR) were performed for each diet treatment. RESULTS: D. rerio fed the SCP containing diet had body weight gains equivalent to the D. rerio fed fish protein, and females had significantly lower total carcass lipid, indicating reduced adiposity. Reproductive success was similar between treatments. Genes differentially expressed in female D. rerio provided the bacterial SCP compared to females given fish protein were overrepresented in the gene ontologies of metabolism, biosynthesis of cholesterol precursors and products, and protein unfolding responses. CONCLUSION: These data support the development of an open-source diet utilizing an ingredient that correlates with improved health profiles and reduced variability in notable outcomes.