Aquatic organisms, such as fish, are important indicators of the bioavailability of metals in coastal environments, demonstrating the capacity of different species to bioaccumulate these metallic elements. The fluvial-lagoon system of the Palizada River is an important ecosystem for its terrestrial and aquatic biological diversity where fishing is an important productive activity in this system. The objective of this research was to evaluate the concentration of Pb and Cd in the muscle tissue of native and invasive fish species in this area. For this, the digestion of fish muscle samples was carried out with a CEM MARS 5 Digestion Microwave System, while the quantification of metals was performed with an atomic absorption equipment. All analysis muscle samples from native and invasive fish showed Pb and Cd in their content. By sampling site there was a statistically significant difference (p < 0.05), with a maximum Pb concentration of 7.760 µg g−1 at the LLAR site (Laguna Larga). In terms of species, the maximum Cd concentration was obtained in the Cyprinus carpio with 6.630 ± 0.127 and in Pterygoplichthus pardalis with 6.547 ± 0.873 µg g−1 (dry weight). The presence of metals such as Pb and Cd in muscle tissue of native and invasive fish species represents an important bioindicator of environmental exposure in the study area and a potential risk to public health, as these species are commonly consumed.