Microcystin-LR (MCLR), one of the most popular microcystins (MCs) found in many field water bodies around the world, poses great health risks to animals and humans. In the present study, healthy common carp (initial weight 24.8 ± 2.3 g) were randomly assigned to five groups. Group I was fed on normal diet as control. Group II was maintained on normal diet and received MCLR intraperitoneal injection (150 μg kg BW). Common carp in groups III, IV, and V were daily pretreated with L-carnitine (LC) at doses of 0.5, 1.0, and 2.0 g kg of the diet for 4 weeks prior to MCLR intraperitoneal injection. The results showed that MCLR alone led to a significant downregulation in immune response, including serum complement C3, lysozyme, and bactericidal activity. However, oxidative stress response: catalase (CAT), superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GPx), and lipid peroxidation (LPO) levels were significantly increased. Similarly, gene expressions of inflammatory IL-1β, TNF-α, IFN I, and heat shock proteins (HSP70 and HSP90) were also upregulated after challenged with MCLR. However, LC pretreated group caused a significant elevation in immune response (C3, lysozyme, and bactericidal activity) and gene expressions of inflammatory IL-1β, TNF-α, IFN I, and heat shock proteins (HSP70 and HSP90) after MCLR stress. Antioxidant activities (CAT, SOD, GSH, GPx, and LPO) were returned to background levels at 96 h after MCLR challenge. Strikingly, LC supplementation at 2.0 g kg has been considered the optimum for common carp since it exhibited enhancement of immune response and antioxidant activity over the level 0.5 and 1.0 g kg, and even better than that of control level. It was concluded that LC as a functional feed additive significantly inhibited the progression of MCLR-induced immunotoxicity and oxidative stress in common carp.