Simple SummaryThe inclusion of phytochemicals in animal diets is a strategy that has been used to improve animal productivity by increasing the production yield. The addition of red-hot pepper (RHP) powder enhances productive rabbit performance and immunological, biochemical, and antioxidant statuses. Rabbits fed 2% RHP powder had higher weights. Thus, adding 1 or 2% RHP powder to rabbit diets is an easy, simple, and safe option for producers. The slaughter index and physical blood characteristics red blood cells (RBC’s), packed cell volume (PCV), hemoglobin (Hb), mean corpuscular volume (MCV), mean corpuscle hemoglobin (MCH) and mean corpuscle hemoglobin concentration (MCHC) were significantly improved by feeding growing rabbits on RHP levels. Low-density lipoprotein-cholesterol (LDL-C) and very-low were distinctly (VLDL-C) decreased (p < 0.05) when feeding rabbits either 1 or 2% RHP supplemented diets. Furthermore, supplementing the rabbit’s diet with 1% RHP led to a significant increase (p < 0.001) in the total antioxidant capacity when compared to the rabbits fed with the basal diet. Additionally, the thyroxin concentration was increased with RHP supplementation. A remarkably significant effect on serum and hepatic oxidative stress responses was observed with RHP supplementation.Animals fed with a high amount of a wide range of antioxidants in their diet are significantly protected against oxidative stress. Powerful antioxidant substances such as vitamin E, vitamin C, and carotenoids are present naturally in red-hot pepper (RHP). This study hypothesized that using RHP may provide protection against oxidative stress and enhance animal physiological responses. Thus, this study aimed to investigate the effect of feeding New Zealand white rabbits with RHP-supplemented diets on their physiological and biochemical responses. New Zealand White rabbits (age = 6 weeks, n = 48) were split equally into three groups (n = 16 in each group). One group was fed a basal diet only (control group), with the other two groups fed a basal diet along with 1 and 2% RHP. Mass spectrometric analysis for the RHP methanolic extract showed some phenolic compounds, such as p-coumaric, sinapinic acids, vanillic, and luteolin, as well as catechin and its isomers. Hepatic antioxidant enzymes (SOD, GSH, GSH-Px, and CAT) were significantly elevated (p < 0.05) by feeding rabbits diets supplemented with 1 or 2% RHP. The addition of RHP significantly enhanced immune-responses; phagocytic activity, chemotaxis, TIg, IgG, IgM, and IgA increased when growing rabbits were fed RHP compared with the control group. In conclusion, dietary supplementation of 1 or 2% RHP may play a role as an enhancer of growth and immune response in growing rabbits.