Acrylamide (ACR), with high prevalence in starchy food, has been associated with the development of several organ toxicities such as immunotoxicity. This study aimed to demonstrate the role of oxidative stress and apoptosis as the mechanisms involved in ACR-induced immunotoxicity in mice. Mice were randomly assigned to six groups and treated as follows: control (normal saline), cyclophosphamide (200 mg kg–1), ACR groups (12.5, 25 and 50mg kg–1, orally), and L-carnitine (L-CAR; 100 mg kg–1) + ACR (50 mg kg–1). After 30 days of exposure, mice were killed and immunotoxic response was evaluated via immune blood cells count and body/organ weights. Oxidative stress parameters and pathological examination were done in thymus and spleen. Also, the apoptosis was evaluated via flow cytometric by annexin V/FITC kit in the splenocytes. Our results indicated that ACR could induce immunotoxicity characterized by reduction in immune blood cells, body/organ weights, and pathological changes in spleen. The assessment of oxidative stress markers revealed increase in lipid peroxidation, protein carbonyl content, and depletion of glutathione level. Also, increased apoptosis was observed in splenocytes after ACR administration compared to the control group. These alterations were markedly normalized by coadministration of L-CAR (as a potent antioxidant). Taken together, the results of this study showed the potential of ACR to induce immunotoxicity through provoking oxidative stress and inducing apoptosis and the protective effect of L-CAR to attenuate this toxicity. These findings will help in elucidating the toxicity mechanism induced by ACR.