Microplastics (MP) can act as carriers of other contaminants, such as metals, including the metalloid arsenic (As). So, the objective of this study was to evaluate the combined effect of MP and As on the polychaete Laeonereis culveri. The animals were divided into four experimental groups: (1) exposed to MP (40 μg/L, polystyrene, 1.1 μm, spherical), (2) exposed only to As (50 μg/L as arsenite), (3) exposed to both MP and As (same concentrations as cited above), and (4) a control group (only water). The animals were exposed for 7 days and parameters related to oxidative stress and energy metabolism, as well as total arsenic content and chemical speciation, were analyzed. The results showed that coexposure to MP and As induced a decrease in GPx and GST activities, while GSH levels were reduced in the group exposed only to microplastics. MP did not induce changes in As accumulation nor did it affect As metabolization capacity. Coexposure to As and MP resulted in elevated glucose levels, lactate concentrations, and LDH activity. Hence, our findings imply that the combination of As and MP may induce a prooxidant environment in L. culveri. Such conditions could potentially compromise other long-term physiological functions.