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Microplastics (MP) are vectors for other environmental contaminants, such as metals, being a considerable problem, especially in the aquatic ecosystem. To investigate the combined effects of MP (high density polyethylene) with lead (Pb), we exposed the mangrove fiddler crab Minuca vocator to Pb (50 mg L -1 ), and MP (25 mg L -1 ) alone and in mixture, for 5 days. We aimed to determine Pb and MP bioaccumulation, as well as physiological (oxygen consumption and hemolymph osmolality) and biochemical (superoxide dismutase, catalase, glutathione peroxidase, and lipid peroxidation) traits effects. Co-exposure of MP and Pb significantly increased the bioaccumulation of Pb, but reduced MP tissue accumulation. Regarding the physiological traits, increasing osmolality and oxygen consumption rates compared to the control were observed, particularly in the combined Pb and MP exposure. As to biochemical traits, the combination of Pb and MP induced the most significant responses in the enzymatic profile antioxidant enzyme activity. The catalase (CAT), glutathione peroxidase (GPx), and dismutase superoxide (SOD) decreased compared to individual exposure effects; the combination of MP and Pb had a synergistic effect on promoting lipid peroxidation (LPO). The co-exposure of MP and Pb acted synergistically when compared to the effects of the isolated compounds. Due to the increasing MP contamination in mangroves, more severe physiological and biochemical effects can be expected on mangrove crabs exposed to metal contamination., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)