The experiment was implemented to assess the influence of dietary supplementation of laying quails with creatine monohydrate (CrM), L-carnitine (CAR) and their mixture (CrMCAR) as antioxidants against oxidative stress (OS) induced by 2.5 ppm lead acetate (LA) in drinking water on productive, physio- logical and microbial aspects. In total, 400 laying quail females at 10 wk of age were divided into a randomized design with 5 groups and 4 replicates of 20 birds each. Birds were fed ad libitum with a balanced diet for 8 wk. The control group was kept under no-stress conditions and was given fresh water without any additives (G1). While birds in other groups were exposed to OS induced experimentally by 2.5 ppm LA in drinking water with no feed additive (G2) or supplemented with 500 mg/kg CrM (G3) or 500 mg/kg CAR (G4) or combination of 250 mg/kg each of CrM and CAR (CrMCAR, G5) to feed mixture. Compared to G2, G5 demonstrated the reduction (P ≤ 0.05) of feed conversion ratio, feed intake, mortality and ileal total coliform, as well as serum and egg malondialdehyde and serum lipid hydroperoxide, uric acid, glucose, cholesterol, enzymatic activities (alanine aminotransferase, aspartate transaminase, alkaline phosphatase, creatine phosphokinase, g-glutamyl transferase), and heterophils/lymphocytes ratio. In the meanwhile, there was an increase (P ≤ 0.05) in egg pro- duction, egg mass, and weight with the improvement of egg quality, serum sex hormones level and ileal lactic acid bacteria for G5 followed by G4 and G3. Moreover, G5 enhanced (P ≤ 0.05), the total antioxidant capacity of egg and serum glutathione, superoxide dismutase, catalase, glutathione peroxidase, protein and calcium levels. Therefore, dietary CrMCAR, CAR and CrM have analogous influence to control by improving the antioxidant and physiological parameters which resulted in better productive performance and egg characteristics of stressed quails. These antioxidants, especially in their equal combination, are beneficial to alleviate oxidative stress incidence and can be recom- mended for poultry feeding under various aspects of environmental stresses.