The effects of ibuprofen (IBU) on the immune parameters of the clam Ruditapes philippinarum were investigated after a 7-day exposure to sublethal IBU concentrations (0, 0 + ethanol, 100, 500, and 1000 μg/L). Total haemocyte count (THC), haemocyte diameter and volume, haemocyte proliferation and uptake of the vital dye Neutral Red (NR) were measured. The cytotoxicity (assessed by the lactate dehydrogenase assay, LDH) and the capability of IBU to induce DNA fragmentation (indicative of apoptosis) were also investigated. The exposure of clams to the highest IBU concentration significantly reduced their THC, whereas no significant changes were observed in either the diameter or volume of haemocytes. Significant increases in haemocyte proliferation were recorded in clams that were exposed to the two highest tested concentrations of IBU. Exposure of clams to 1000 μg IBU/L significantly reduced NR uptake and increased haemolymph LDH activity. Conversely, IBU did not induce DNA fragmentation in haemocytes. Although the IBU concentrations tested in this study were higher than those generally recorded in aquatic environments, results obtained indicate that exposure of clams to IBU induces significant alterations in the immune parameters and suggest potential immunosuppression in treated clams.