BACKGROUND: This study emphasizes evaluating the antiemetic efficacy of the natural food component caffeic acid (CAF) using a copper sulfate pentahydrate (CuSO METHODS: Two doses (25 and 50 mg/kg b.w.) of CAF and several referral drugs considered positive controls (PCs), including domperidone (6 mg/kg), hyoscine (21 mg/kg), aprepitant (16 mg/kg), diphenhydramine (10 mg/kg), and ondansetron (5 mg/kg), were orally administered to chicks. The vehicle served as the control group. Co-treatments of CAF with referral drugs were also provided to chicks to evaluate the modulatory action of the test compound. RESULTS: According to the results, CAF delayed the emetic onset and decreased the frequency of retches in a dose-dependent manner compared to the vehicle group. CAF (40 mg/kg) represented a notable delayed latency period (60.17 ± 3.16 s) and a diminished number of retchings (18.33 ± 1.74 times) compared to the control group. Further, in the co-treatments, CAF increased the latency period and reduced the number of retches, except for domperidone. In the in silico investigation, CAF showed notable binding affinity toward the D CONCLUSION: This research indicated that CAF has mild antiemetic properties by interacting with the D