Lutein, a dihydroxycarotenoid, has antioxidant and immunomodulatory potential. Two 2 x 2 x 2 factorial designs examined effects of carotenoids during in ovo embryogenesis and, in the diet posthatch, on the systemic inflammatory response to lipopolysaccharide (LPS). In both trials, breeder hens were fed a carotenoid-replete (40 mg lutein/kg) or a carotenoid-deplete diet, eggs were collected, and chicks were hatched from carotenoid-deplete or carotenoid-replete eggs. Meat-type chicks (n = 160 and n = 144, respectively) were then fed diets containing 0 or 40 mg lutein/kg diet and either injected or not injected with LPS. LPS injection increased plasma haptoglobin and Zn (P < 0.01) and reduced plasma Fe and Cu (P < 0.01). Chicks hatched from carotenoid-deplete eggs had greater changes in plasma Fe and S post-LPS than chicks hatched from carotenoid-replete eggs (P < 0.05 for each). Compared with chicks fed 40 mg lutein/kg diet, chicks fed 0 mg lutein had greater body weight losses and higher plasma haptoglobin and relative thymus, bursa, and spleen weights post-LPS (P < 0.05). Data suggest that a lack of carotenoid exposure, either in ovo or posthatch, increases parameters of systemic inflammation.