The ubiquitous presence of pentachlorophenol (PCP) in ocean environments threatens marine organisms. However, its effects on immunity of marine invertebrates at environmentally realistic levels are still largely unknown. In this study, the immunotoxicity of PCP to a representative bivalve species was evaluated. In addition, its impacts on metabolism, energy supply, detoxification, and oxidative stress status were also analysed by physiological examination as well as comparative transcriptomic and metabolomic analyses to reveal potential mechanisms underpinning. Results illustrated that the immunity of blood clams was evidently hampered upon PCP exposure. Additionally, significant alterations in energy metabolism were detected in PCP-exposed clams. Meanwhile, the expressions of key detoxification genes and the in vivo contents (or activity) of key detoxification enzymes were markedly altered. Exposure to PCP also triggered significant elevations in intracellular ROS and MDA whereas evident suppression of haemocyte viability. The abovementioned findings were further supported by transcriptomic and metabolomic analyses. Our results suggest that PCP may hamper the immunity of the blood clam by (i) constraining the cellular energy supply through disrupting metabolism; and (ii) damaging haemocytes through inducing oxidative stress. Considering the high similarity of immunity among species, many marine invertebrates may be threatened by PCP, which deserves more attention.