Crossbreeding has emerged as a strategy to combine desirable traits from different sheep breeds, with the goal of enhancing productivity, disease resistance, and growth rates. This study compares the immune responses, rumen microbiomes, and serum metabolites of Hu sheep, East Friesian (EF) sheep, and crossbred Hu × EF (DH) sheep to explore the effects of crossbreeding on productivity and disease resistance. Hu sheep exhibited significantly higher lymphocyte counts (p