This study evaluated the efficacy of sodium heptanoate (HEPT’ON) or sodium butyrate (GUSTOR BP70; Norel S.A.) against ETEC K88 in weanlings. A total of 72 3-week-old piglets were divided into 24 pens and 3 experimental groups: Plain diet (CTR); supplemented with GUSTOR BP70 (BUT); or supplemented with HEPT’ON (HPT), both at 3 kg/t and containing 70% of acid salt protected with vegetable fat. Intake and weight were monitored along 15 d. After one week, animals were orally inoculated with ETEC K88 (1x10⁹ cfu) and fecal consistency and rectal temperature evaluated afterward. On d 4 and 8 post inoculation (PI) one animal per pen was euthanized to evaluate inflammatory response (TNFα and Pig-MAP) and counts of enterobacteria and E. coli in ileal-colonic contents and ileal mucosa scrapes. No significant differences were seen in performance although numerical values were higher for the experimental diets (217, 264 and 243 g ADFI and 117, 123 and 124 g ADG for CTR, BUT and HPT). No significant differences were found in fecal consistency, rectal temperature and inflammatory markers. Regarding microbiological changes, no significant differences were observed between treatments in the colon. Nonetheless, in ileum digesta, there were numerical differences (P = 0.126) with higher number of enterobacteria in both acids treatments at d 4 PI, that was correlated to an increase in the number of enterobacteria and E. coli recovered from the ileal scrapes (4.30, 5.88 and 5.46 log cfu E. coli for CTR, BUT and HPT, P = 0.003). This increase, however, was not found at d 8 PI when even a decrease in the numerical values of E. coli in ileal digesta was seen for BUT treatment (6.58, 6.01 and 6.93 log cfu for CTR, BUT and HPT, P = 0.036) that also showed a tendency to improve the colonic consistency (P = 0.099). These results suggest the potential of BUT to improve the recovery of the animals after an ETEC challenge. More studies under field conditions with a higher number of animals would be needed to confirm the numerical differences found in performance.