Aim of the study: Despite previous research into mannan oligosaccharides (MOS) and calcium butyrate coated with palm oil (CCB) in poultry, there is a notable gap in the literature regarding the effects of these feed additives, either individually or in combination, on the growth performance, carcass values, blood biochemistry, immune response, and meat quality of growing Japanese quails. Area of study: Türkiye. Material and methods: A total of 168 mixed-sex one-day-old quails were randomly allocated to one of four treatment groups, with each group containing 7 birds per cage. The control group was fed a basal diet, while the treatment groups received the following additives: 1 g/kg of CCB, 2 g/kg of MOS, and a combination of MOS+CCB added to the basal diet, respectively. Main results: None of the treatments had a significant impact on performance, relative organ weights, total protein, albumin, globulin, total cholesterol, high-density lipoprotein cholesterol, and lipoprotein lipase concentrations in blood serum, or humoral immunity on day 28. However, the inclusion of MOS and CCB in the diet, either individually or in combination, increased carcass yield and reduced low-density lipoprotein cholesterol and triglyceride levels in the blood serum. Additionally, these additives helped maintain optimal pH levels and lower malondialdehyde concentrations in the breast meat. Moreover, the combination of MOS + CCB significantly improved water holding capacity and antibody titers against the Newcastle Disease vaccine on day 42 in Japanese quails. Research highlights: The natural feed additives CCB and MOS contribute to enhanced carcass yield, improved meat quality, and strengthened humoral immunity, while simultaneously lowering lipid values in the bloodstream.