19The development of alternatives to antibiotics is crucial to limiting the incidence of antimicrobial 20 resistance, especially in prophylactic and metaphylactic use to control post-weaning diarrhea 21 (PWD). Feed additives, including bioactive compounds, could be a promising alternative. This 22 study aimed to test two bioactive compounds, sodium salicylate (SA) and a chestnut extract 23 (CE) containing hydrolysable tannins, on the occurrence of PWD. At weaning, 72 piglets were 24 assigned to four treatments that combined two factors: CE supplementation (with 2% of CE 25 (CE+) or without (CE-)) and SA supplementation (with 35 mg/kg BW of SA (SA+) or without 26 (SA-)). Then, 4 days after weaning, all piglets were infected with a suspension at 10 8 CFU/ml 27 of enterotoxigenic Escherichia coli (ETEC F4ac). Each piglet had free access to an electrolyte 28 solution containing, or not, SA. This SA supplementation was administered for 5 days (i.e., 29 from the day of infection (day 0) to 4 days post-infection (day 4). During the 2 weeks post-30 infection, supplementation with SA had no effect (P > 0.05) on growth performances nor on 31 fecal scores. A significant SA × time interaction (P < 0.01) for fecal scores and the percentage 32 of diarrhea indicated that piglets with SA did not recover faster and did have a second episode 33 of diarrhea. In contrast to SA treatment, inclusion of CE increased (P < 0.05) growth 34 performances and feed intake. In the first week post-infection, CE decreased (P < 0.001) the 35 overall fecal scores, the percentage of piglets with diarrhea, the days in diarrhea, and ETEC 36 shedding in the feces. There was a SA×CE interaction (P < 0.05) for ETEC shedding, 37 suggesting a negative effect of combining SA with CE. This study highlighted that, in contrast 38 to SA, CE could represent a promising alternative to antibiotics immediately after weaning for 39 improving growth performance and reducing PWD. 41 Post-weaning diarrhea (PWD) is a major enteric disease in pig production that occurs mainly 42 during the first two weeks after weaning. This problem causes substantial economic losses 43 due to high rates of mortality and morbidity, depression of feed intake and growth, and 44 increased costs of medication [1]. 45 Apart from the multifactorial etiology owing to several stressors, including nutritional, social, 46 and environmental changes, PWD is often related to infection with specific pathogens. 47 Enterotoxigenic Escherichia coli (ETEC) is a prevalent pathogen involved in PWD [2]. For 48 instance, in Switzerland, 42.5% of weaned pigs with diarrhea were identified as having ETEC 49 [3]. Those bacteria possess fimbriae that adhere to receptors located on the apical side of the 50 enterocytes and secrete enterotoxins, including heat labile toxin (LT) and heat stable toxin 51 (STb), which results in fluid secretion into the intestinal lumen, leading to dehydration and 52 acidosis, which ultimately results in diarrhea [4, 5]. 53 Antibiotics are usually used to treat this type of infection....