BACKGROUND: Approximately, one-third of dairy cows suffer from postpartum diseases. Ketosis is considered an important inducer of other postpartum diseases by disrupting energy metabolism. Although the rumen microbiome may be involved in the etiology of ketosis by supplying volatile fatty acids, the rumen environmental dynamics of ketosis cows are unclear. Using multi-omics, this study aimed to elucidate changes in the rumen microbiome during parturition of ketosis cows and the association between the rumen microbiome and host energy metabolism. The study included 810 rumen content samples and 789 serum samples from day - 21 and 21 relative to calving day from 61 ketosis cows and 84 healthy cows. RESULTS: In ketosis cows, the rumen bacterial composition after parturition changed dramatically and needed a longer time to restore. The molar proportions of propionate were lower in ketosis cows than those in healthy cows on days 3 and 7 and negatively correlated with the serum β-hydroxybutyrate (BHBA) levels. The fermentation sub-pathway of propionate metabolism and partial glucogenic amino acid pathways were downregulated on day 3. Prevotella, UBA1066, and microbiota diversity indices regulate serum BHBA and glucose (GLU) levels via arginine, alanine, glycine, or propionate. Propionate administration to ketosis cows potentially decreased the serum BHBA concentration. CONCLUSIONS: Collectively, we found rumen disruption happened after calving among ketosis cows, and insufficient glycogenic substrates, such as propionate, may be related to ketosis development. The study findings have implications for the relationship between rumen microbiome dynamics and host energy metabolism, which lays the foundation for the future rumen microbiome investigation for improving postpartum management in cows. Video Abstract.