It is a long-recognized fact that marine plastic debris contaminates the oceans and seas of the entire world. Even though their effects on the aquatic biota are not well documented or understood. The effects of dietary polyvinylchloride microparticles (PVC-MPs) on the general health, immune status and some stress markers were studied using gilthead seabream (Sparus aurata) as a model of marine fish. Thirty specimens were randomly placed in three running sea water aquaria and fish in each aquarium received an experimental diet containing 0 (control), 100 or 500 mg kg−1 of PVC-MPs for 30 days. Metabolic parameters in serum indicated that the dietary intake of PVC-MPs negatively affected several vital organs. Humoral immune parameters were determined in serum and skin mucus. Cellular immune parameters were determined in head-kidney leucocytes. Concomitantly, the expression of different genes related to stress was studied in head-kidney and liver. Regarding head-kidney gene expression, prdx5 was significantly decreased by PVC-MPs intake for 15 and 30 days, respect to the values found in control fish. On the other hand, the expression of prdx1 and prdx3 were significantly increased by the PVC-MPs intake during 15 and 30 days, compared with the values found in control fish. Furthermore, the expression of hsp90 and ucp1 genes decreased and increased, respectively, in the liver of fish fed 500 mg kg−1 of PVC-MPs for 30 days. Although ingestion of PVC-MPs provoked few significant effects (mostly increases) in the main immune activities of gilthead seabream compared with the values found in control fish, PVC-MPs are recognized by the fish as stressors. Continued exposure of fish to high concentrations of PVC-MPs could have a negative impact on fish physiology due to the chronic stress produced.