This study investigated the effects of a phytogenic feed additive (PFA) containing a blend of herbs, plant extracts and essential oils from the Lamiaceae, Schisandraceae, Zingiberaceae and Fabaceae families on the fecal score, intestinal histomorphology and fecal excretion of F4-fimbriated enterotoxigenic Escherichia coli (F4-ETEC) in post-weaning piglets. Thirty 31-day-old weaned piglets were randomly allocated to three treatment groups. The positive control (PC) group received colistin via drinking water from d 8 to 14 post-weaning and the same basal diet as the negative control (NC) group; the treatment group received the basal diet with PFA supplementation (1 g/kg of feed). The experiment lasted 21 days. At day 9 post-weaning, all piglets were orally administered 3.0 × 10¹⁰ CFU/piglet of the F4-ETEC strain. The PC piglets had higher fecal consistency than the NC and PFA piglets. PFA supplementation resulted in a lower percentage of piglets excreting F4-ETEC in the feces on days 4–7 post-challenge than in the NC group (p < 0.05) but a higher percentage versus the PC group on day 3–7 post-challenge (p < 0.05). The number of goblet cells (GCs) in the jejunum of the PFA piglets was higher than the NC and PC piglets (p < 0.01). The GC density in the jejunum of the PFA piglets was larger than in the PC piglets (p < 0.05) and similar to the NC piglets (p > 0.10). Mucus thickness in the jejunum of the PFA piglets was similar to the NC piglets and PC piglets (p > 0.10). In conclusion, PFA supplementation to the F4-ETEC-challenged piglets reduced the prevalence of fecal E. coli excretion and improved jejunal histomorphology.