The common zebrafish (D. rerio) is an important preclinical biomedical model. The developmental, physiological and genomic platforms are well characterized in zebrafish, consequently, zebrafish can be used in understanding health related impacts of novel and sustainable feed ingredients with results directly translatable to humans. In an effort to assess the impact of sustainable bacterial single cell protein ingredient replacement for fish protein on zebrafish, we conducted a 14-week feeding trial on 31-day post fertilization zebrafish (10 tanks per diet, 5 fish per liter density). Zebrafish growth was assessed every 2 weeks during the feeding trial and at study termination fish were assessed for body composition, reproduction, and female liver expression (RNAseq with confirmatory rtPCR). Male and female zebrafish had no differences in terminal body weight, though female body lipid content was reduced in the bacterial protein diet. There were no differences between diets for reproduction based on spawning success, total eggs produced, or egg viability 24 hours post fertilization. Female RNAseq results for fish receiving the bacterial source protein (limited to the top 15% of expressed genes), found 43 differentially expressed genes (22 down-regulated, 21 up-regulated) with impacted gene ontologies related to cholesterol biosynthesis, metabolism, and protein processing in the endoplasmic reticulum. Expression changes are hypothesized to be related to the beta glucan content of the bacterial protein source, which can impact cholesterol and bile acid homeostasis. These data can support development of sustainable open-source diets for the zebrafish community