In an experimental trial lasted 102 days started from the age of 4 days after birth to the weaning age (105 days) conducted to compare the effect of Co-enzyme Q10 (CoQ10) and L-Carnitine (L-Ca)on growth, physical and chemical blood indices immunity, and antioxidant status of newborn Egyptian buffalo calves. Fifteen calves with 36.13±0.86Kg initial live body weight (LBW) were allocated into three groups where calves in the first group received no treatment (control group, Ctrl). The calves in the second and the third groups received 40 mg L-Ca/kg LBW and 10 mg CoQ10/kg LBW, respectively as daily oral doses. Significant differences in weight gain among treatments starting from the age of 60 days where the CoQ10 and L-Ca groups were higher than the control. Blood physical parameters of all experimental animals show no abnormal cases and no alteration in hematological indices among groups were recorded. Meanwhile, blood biochemical contents were varied significantly (P<0.05) among groups, where the control group gave the highest values of glucose, total lipids, total cholesterol, triglyceride, ALT, AST, ALP, T3, and T4compared to the other groups. Moreover, the CoQ10 group exhibited the highest significant (p<0.05) contents of TP and the lowest T3 and T4 values. Furthermore, the highest values of lysozyme and bactericidal activities were recorded in the CoQ10 group compared to the other groups. Both CoQ10 and L-Ca groups showed higher superoxide dismutase (SOD) and catalase (CAT) contents than control. In conclusion, CoQ10 or L-Ca supplements improve growth, immunity and antioxidant contents.