This study aimed to evaluate the effects of coated zinc oxide supplementation on growth performance, fecal scores, blood profiles, intestinal and fecal microbial shedding, and small intestinal morphology in young pigs challenged with enterotoxigenic Escherichia coli (ETEC) K88. Sixty crossbred (Duroc × [Yorkshire × Landrace]) weaning pigs with an average initial body weight (BW) of 6.56 ± 0.89 kg (28 ± 2 days of age) were randomly allotted to 6 treatment groups (5 replicate pens per treatment with 1 barrow and 1 gilt per pen) on the basis of initial BW. The six experimental treatments were: (1) pigs fed basal diets and unchallenged with ETEC K88 (NC-U); (2) pigs fed basal diets and challenged with ETEC K88 on day 22 (NC-C); (3) pigs fed basal diets supplemented with 2500 mg/kg conventional zinc oxide and challenged with ETEC K88 on day 22 (PC); (4) pigs fed basal diets supplemented with 500 mg/kg coated zinc oxide challenged with ETEC K88 on day 22 (CZO500); (5) pigs fed basal diets supplemented with 750 mg/kg coated zinc oxide challenged with ETEC K88 on day 22 (CZO750); (6) pigs fed basal diets supplemented with 1000 mg/kg coated zinc oxide challenged with ETEC K88 on day 22 (CZO1000). Pigs in PC and CZO1000 treatments had increased (P < 0.05) average daily gain (ADG) and gain to feed ratio (G:F) compared with those in NC-U, NC-C, CZO500, and CZO750 diets in pre-challenge period. In post-challenge period, pigs from NC-C treatment had lower (P < 0.05) ADG and G:F compared with pigs from PC, NC-U, CZO750, and CZO1000 treatments. Pigs in CZO500, CZO750, and CZO1000 treatments had lower (P < 0.05) fecal zinc compared with those in PC treatment. Serum interleukin-6 and tumour necrosis factor-α concentrations in pigs from NC-U, PC, and CZO1000 treatments was less (P < 0.05) than those of pigs from NC-C treatment. At day 3 post-challenge, pigs in PC and CZO1000 treatment groups had higher (P < 0.05) duodenal and ileal villus height and villus height to crypt depth ratio compared with those in NC-C treatment group. In conclusion, administration of low dose (1000 mg/kg) of coated zinc oxide exerted similar effects on alleviating the decrease in growth performance, controlling the severity of diarrhea, reducing the inflammation response, and mitigating the deterioration of intestinal morphology induced by ETEC K88 challenge in young pigs as pharmacological level of conventional zinc oxide.