The effects of Saccharomyces cerevisiae fermentation product on rumen microbiome composition and function were studied in 8 rumen-cannulated lactating cows in a crossover study with two 5-wk periods. Each period consisted of a 4-wk normal feeding and a 1-wk grain-based SARA challenge. A 3-wk washout period separated the experimental periods. During each period, 4 cows received 14 g/d of SCFP (Original XPC, Diamond V) mixed with 126 g/d ground corn and the other 4 received 140 g/d ground corn as control. Rumen fluid was collected during wk 4 and 5 of each period. Genomic DNA was extracted and subjected to shotgun metagenomic sequencing using a MiSeq Illumina platform. Host genomic sequences were removed before analysis. Taxonomies were annotated against Greengenes database and functional genes were annotated against SEED subsystems in the MG-RAST pipeline. Both compositional and functional differences among treatments were analyzed by the linear discriminant analysis effect size. In total, 103.4 GB sequences were obtained from 32 shotgun metagenomic samples with an average of 10 millions sequences per sample. The SCFP supplement altered the β-diversity of rumen functional metagenome under both control and SARA conditions (P < 0.05). The SCFP supplement restored several cellulolytic populations, including Fibrobacteres, Paenibacillaceae and Spirochaetaceae, as well as Burkholderiales that were suppressed during SARA (P < 0.05). The SCFP supplement also tended to increase the population of Eubacteriaceae, Coriobacteriaceae and unclassified Clostridiales observed during SARA (P < 0.05). Several enzymatic pathways were downregulated during SARA. The SCFP supplement increased the abundance of formate dehydrogenase and methylmalonyl-CoA mutase (MCM) that were suppressed during SARA (P < 0.05). The MCM is a vitamin B12-dependent enzyme constantly found in methanol-utilizing bacteria, such as members of Burkholderiales. Data reveals potential mechanisms through which SCFP supplement contributes to the resilience of the rumen microbiome, especially during SARA.