This study was conducted to evaluate the effects of feeding diets supplemented with spay-dried whole egg containing anti-F4 antibodies (SDWE) against recombinantly produced F4 antigens to piglets challenged with enterotoxigenic Escherichia coli K88 (ETEC). Twenty-seven individually housed piglets [(Yorkshire × Landrace) × Duroc, 7.27 ± 0.47 kg initial BW] weaned at 21 ± 1 d were randomly allotted to 3 dietary treatments (n = 9) consisting of a wheat-soybean meal basal diet containing either 0 (control egg powder; CEP), 0.1% (SDWE1) or 0.4% (SDWE2) SDWE for a 14-d study. After a 7-d adaptation period, all pigs were weighed, blood samples collected and then orally challenged with 6 mL (2 × 10⁹ cfu/mL) of freshly grown ETEC inoculum on d 8. Pigs had ad libitum access to feed and water throughout the study. Blood was sampled at 24 h and 48 h post-challenge to determine plasma urea nitrogen (PUN) content 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 villus height and crypt depth measurements. During the pre-challenge period, pigs fed the SDWE2 diet had higher (P < 0.05) ADG and G: F compared with CEP but there were no differences among treatments in any of the performance response criteria during the post-challenge period. Incidences of diarrhea were similar among treatments although piglets fed SDWE-containing diets recovered from diarrhea within 48 h (with fecal consistency score of 0.0) of ETEC compared with CEP pigs. Also, fecal shedding of ETEC, PUN content and intestinal histomorphology were similar among treatments. The results show that SDWE at 0.4% supported greater piglet performance before challenge although there was no benefit of SDWE supplementation at either 0.1% or 0.4% evident during the post-challenge period.