The effects of cadmium (Cd) and arsenic (As), dosed alone or in combination have been poorly investigated in crustaceans. Besides, it is not known if dietary supplementation of exogenous antioxidants, like lipoic acid (LA), might prevent or even reverse toxic effects of Cd and As. The objective of present study was to evaluate the role of lipoic acid in modulating biochemical responses after Cd and As exposure in Litopenaeus vannamei. Muscle from shrimp exposed to Cd alone or Cd+As there was a decrease in glutathione (GSH) levels, while the pre-treatment with LA reversed this situation. In this tissue, the pre-treatment with LA also induced an increase in glutathione-S-transferase (GST) activity in all groups. In hepatopancreas it was observed a marked accumulation of Cd and As, a decrease in the reactive oxygen species (ROS) concentration in response to Cd exposure alone (-LA); concomitant in the same group it was observed an increment of metallothioneins-like content. As exposure induced an increase in GSH levels but LA reversed this increase. Also, LA showed to increase the GST activity in all groups treated. Besides, in this organ LA showed to augment total antioxidant competence. Obtained results indicate that LAcan be used as a chemo protectant against oxidative insults in shrimp.