ABSTRACT: This study aimed to determine the effects of early antibiotic intervention (EAI) on subsequent blood parameters, apparent nutrient digestibility, and fecal fermentation profile in pigs with different dietary crude protein (CP) levels. Eighteen litters of piglets (total 212) were randomly allocated to 2 groups and were fed a creep feed diet with or without in-feed antibiotics (olaquindox, oxytetracycline calcium and kitasamycin) from postnatal d 7 to d 42. On d 42, the piglets within the control or antibiotic group were mixed, respectively, and then further randomly assigned to a normal- (20%, 18%, and 14% CP from d 42 to d 77, d 77 to d 120, and d 120 to d 185, respectively) or a low-CP diet (16%, 14%, and 10% CP from d 42 to d 77, d 77 to d 120, and d 120 to d 185, respectively), generating 4 groups. On d 77 (short-term) and d 185 (long-term), serum and fecal samples were obtained for blood parameters, microbial composition and microbial metabolism analysis.EAI increased (P < 0.05) albumin and glucose concentrations in low-CP diet on d 77, and increased (P < 0.05) urea concentration in normal-CP diet. On d 185, EAI increased (P < 0.05) globulin concentration in normal-CP diets, but decreased glucose concentration. For nutrient digestibility, EAI increased (P < 0.05) digestibility of CP on d 77. For fecal microbiota, the EAI as well as low-CP diet decreased (P < 0.05) E. coli count on d 77. For fecal metabolites, on d 77, EAI decreased (P < 0.05) total amines concentration but increased skatole concentration in low-CP diet. On d 185, the EAI increased (P < 0.05) putrescine and total amines concentrations in low-CP diets but reduced (P < 0.05) in the normal-CP diets. The low-CP diet decreased the concentrations of these compounds.Collectively, these results indicate that EAI has short-term effects on the blood parameters and fecal microbial fermentation profile. The effects of EAI varied between CP levels, which was characterized by the significant alteration of glucose and putrescine concentration.