Experimental results showed that the gill monogenean Cichlidogyrus sclerosus and its host, the Nile tilapia Oreochromis niloticus, exhibited significant numerical and physiological responses after exposure to sediments polluted with polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls, and heavy metals in comparison with control fishes. After 15 days of exposure, C. sclerosus abundance significantly increased in treatments with low to fairly high sediment pollutant concentrations, but declined at high sediment pollutant concentrations. Hypertrophy and hyperplasia in secondary gill lamellae and the spleen melanomacrophage centers were significantly higher at extremely high sediment pollutant concentrations compared with the controls. Spleen lymphocyte and monocyte counts were significantly lower at extremely high sediment pollutant concentrations and were significantly correlated with high fluorescent aromatic compound concentrations measured as PAH exposure indicators. A multivariate redundancy analysis showed significant statistical association between sediment pollutant concentration, C. sclerosus abundance, and tilapia physiological variables. The polluted sediments negatively affected monogenean abundance and induced immunosuppression in hosts, consequently increasing histological damage in hosts and allowing persistent C. sclerosus infection. This study documents evidence suggesting that C. sclerosus and its host are indeed excellent models to test environmental quality in tropical freshwater ecosystems.