This study was conducted to investigate the effect of dietary energy concentration on growth performance, serum biochemical indices, and the mRNA expression of inflammatory cytokines in the liver of meat ducks challenged with lipopolysaccharide (LPS). A total of 600 1-d-old Cherry Valley meat ducks were randomly assigned to 10 treatments with six replicate cages of 10 birds/pen. A 5 × 2 factorial arrangement in a complete randomized design experiment was used to study the effect of five concentrations of dietary metabolizable energy (ME, 2,800, 2,900, 3,000, 3,100, and 3,200 kcal/kg) with or without a challenge with LPS in meat ducks. All experimental ducks were intraperitoneally injected with either 0.5 mg/kg body weight (BW) LPS or an equivalent amount of sterile saline at 15, 17, and 19 d of age. The results showed that LPS challenge significantly decreased (P < 0.05) BW (d 21), body weight gain (d 15-21) and average daily feed intake (ADFI; d 15-21), and markedly increased (P < 0.05) relative spleen weight, serum total protein concentration, and the mRNA expression of interleukin 6 (IL-6), interleukin 10, transforming growth factor β (TGF-β), and Avian Beta Defensin 10 (AVBD-10) in the liver of meat ducks. Ducks fed 3,200 kcal/kg ME diet had the lowest (P < 0.05) ADFI than those fed with the other diets. Additionally, there were significantly LPS by diet interactions on IL-6, interferon-γ, TGF-β, AVBD-10, and inducible nitric oxide synthase mRNA expression (P < 0.05), wherein a more pronounced liver inflammatory response was observed in birds fed high-energy diets (3,100 and 3,200 kcal/kg ME) than birds fed low-energy diet (2,800 and 2,900 kcal/kg ME). The results indicated that 3,100 and 3,200 kcal/kg ME of diets increased hepatic inflammatory markers induced by LPS challenge in ducks but did not influence performance responsiveness during this challenge.