This study was to evaluate the effect of daily oral administration of N-acetylcysteine (NAC), L-carnitine (L-C), or their Combination for 2 months pre-semen collection on semen quality, sexual desire and some blood parameters traits of Egyptian buffalo bulls. A total of 20 bulls (400±37 kg LBW and 24-25 mo old) were divide into 4 groups. In group1 (G1, control), G2, G3 and G4, animals fed a basal ration and the managed under the same conditions, and were received orally a daily dose of 0, 3 L-C, 3 g NAC, or 1.5 g NAC +1.5 g L-C as a combination/bull/day, respectively, for 2 months. The results showed that bulls that received the combination dose (G4) increased (P<0.05) the concentration of total proteins, albumin, globulin and glucose, while it decreased (P<0.05) total cholesterol, triglyceride, creatinene concentrations, and AST and ALT activities compared with the control and other groups. All physical characteristics in fresh and thawed semen were higher (P<0.05) in all treated groups than in the control group, being the best in G4. Plasma testosterone and total antioxidant capacity concentrations were increased (P<0.05) in G4, G3 and G2 compare with the control (G1), being the best for G4 bulls. In conclusion, an oral dose of 1.5 g NAC plus 1.5 g L-C bull/day, as a combination, for 2 months pre-semen collection improves health status, immunity response and antioxidant capacity of buffalo bulls to produce semen with high quality require for spreading the tool of artificial insemination in buffaloes.