The aim of this study was to investigate the combined effects of chitosan oligosaccharide (COS) and a microencapsulated Enterococcus faecalis probiotic (PRO) on growth performance and diarrhea incidences in enterotoxigenic Escherichia coli K88 (ETEC) challenged piglets in a 14-d study. Thirty piglets [(Yorkshire × Landrace) × Duroc], 7.19 ± 0.52 kg initial BW weaned at 21 ± 1 d were allotted to 5 treatment groups (n = 6) consisting of a corn-soybean meal diet with no additive (negative control, NC), the NC + 0.25% chlortetracycline (positive control, PC), NC + 400 mg/kg COS (COS), NC + 100 mg/kg PRO (PRO) and NC + a combination of COS and PRO (CPRO). The basal diet was formulated to meet the NRC (2012) nutrient specifications for 5 to 10 kg BW pigs. Pigs were individually housed in cages, acclimated to treatments for a 7-d period and had ad libitum access to feed and water throughout the study. On d 8, pigs were weighed, blood samples were collected and then orally challenged with 6 mL (1 × 10¹¹ cfu/mL) of freshly grown ETEC inoculum. Post-challenge, blood was sampled at 24 h and 48 h to determine plasma urea nitrogen (PUN) and diarrhea incidences and fecal consistency scores were recorded from d 9 to d 12. On d 14, all pigs were weighed and then killed to obtain intestinal tissue samples for histomorphometric measurements. Growth performance responses were similar among treatments during the pre- and post- challenge periods. There were no significant differences in PUN content, incidences of diarrhea and fecal consistency scores among treatment. The intestinal histomorphology results did not differ significantly among treatments except for PC with increased (P = 0.0003) villus-crypt ratio compared with the NC. Therefore, under the conditions of the present study, supplementing pig starter diet with 400 mg/kg COS or 100 mg/kg PRO or their combination had no effect against ETEC-induced diarrhea and did not improve growth performance in ETEC challenged piglets compared with control group.