This study determined potential microbial and metabolic biomarkers of feed efficiency in Angus heifers. Seventeen ruminal cannulated Angus heifers underwent a 70-day feed efficiency trial. Residual feed intake was used to determine high and low feed efficient heifers. On day 70 of the trial, rumen content and blood were collected and used for microbial and metabolomic analyses, respectively. Bacterial populations were examined by targeting the V4 region of the 16S rRNA gene and analyzed using QIIME and SAS. Rumen fluid and serum metabolites were analyzed using MetaboAnalyst. No microbial taxa differed after false discovery rate correction, but seven did differ (p ≤ 0.05) prior to correction, including Lachnospiraceae (Other), Desulfobulbaceae, Neisseriaceae, Shuttleworthia, Corynebacterium, p-75-a5, and L7A-E11. No differences were observed in alpha diversity metrics. Beta diversity utilizing unweighted UniFrac distances analyzed via PERMANOVA was significant (p = 0.03). Several metabolites in rumen fluid metabolites were correlated with bacteria that differed by feed efficiency phenotype. The metabolites correlated with bacteria were primarily involved in nutrient signaling and microbial crude protein availability. These data suggest variation in the availability of nutrients, primarily amino acids, as well as a relationship among microbiota, metabolome, and host feed efficiency phenotypes in heifers.