Supplementing feed with different sources of zinc impacts zootechnical performances, the zinc concentration in feces and pathogen excretion in an ETEC infection model in pigs. High doses of zinc oxide (ZnO) are commonly used to prevent and reduce the occurrence of post-weaning diarrhea. Expecting the European Union ban on high doses of ZnO to become effective in 2022, new formulations of ZnO were explored to provide a therapeutic effect at doses accepted by the regulatory authorities. The objective of this study was to assess the efficacy of a potentiated form of ZnO (HiZox, Animine, France) to reduce the severity and incidence of post weaning diarrhea in an enterotoxigenic Escherichia coli F4 (ETEC F4) infection model. Seventy two Swiss Large White piglets (7.7 ± 0.9 kg; 24.9 ± 1.3 days) were weaned and orally infected 4 days later with a solution containing 1010 ETEC F4. Piglets were fed ad libitum with a diet supplemented with the potentiated form of ZnO at 150 and 300 mg/kg zinc (Zn) or a conventional source of ZnO given at 150 or 3000 ppm for 14 days after weaning. Body weight, feed intake and fecal score were monitored throughout the study. The quantity of Zn and ETEC F4 excreted in feces were measured. The potentiated form of ZnO reduced the number of piglets rescue-treated with antibiotics but not the severity or duration of diarrhea. Average daily gain and feed efficiency were also not affected. The quantity of Zn excreted in feces was reduced compared to that in the 3000 mg/kg group (P<0.0001), but not the quantity of ETEC F4. The conventional ZnO given at 3000 mg/kg Zn reduced the severity and duration of diarrhea and improved average daily gain and feed intake, but also increased the quantity of Zn excreted in feces which was 11 times more concentrated than in the other groups.