Technical Abstract: This study investigated the efficacy of trans-cinnamaldehyde (TC) and eugenol (EG) for reducing Salmonella Enteritidis (SE) colonization in broiler chicks. In three separate experiments for each compound, day-old, chicks (N=75/experiment) were randomly assigned to five treatments (n=15/treatment): a negative control (-SE, -TC or EG), a compound control (-SE, +TC or EG at 0.75% or 1%, respectively), a positive control (+SE, -TC or EG), a low dose treatment (+SE, +0.5% TC or 0.75% EG) and a high dose treatment (+SE, +0.75% TC or 1% EG). On day 0, birds were tested for any inherent Salmonella (n=5/experiment). On day 8, birds were inoculated with 8.0 log10 CFU SE by crop gavage, and cecal colonization by SE was ascertained (n=10/experiment) after 24 h. Six birds from each treatment were euthanized on days 7 and 10 after inoculation, and SE populations in the cecum were determined. TC at 0.5 or 0.75%, and EG at 0.75 or 1% consistently reduced SE populations in cecum after 10 days of infection, in all experiments. Feed intake and body weight were not significantly different for TC treatments. However, EG treated birds had significantly lower body weights compared to the control. Follow up in vitro experiments revealed that the sub-inhibitory concentrations (SIC – concentrations that do not inhibit Salmonella growth) of TC and EG reduced motility and invasive abilities of SE, and down-regulated expression of motility genes flhC and motA, and invasion genes hilA, hilD and invF. The results suggest that supplementation of TC and EG through feed can effectively reduce SE colonization in chickens.