Microplastic pollution has been associated with coral susceptibility to disease, yet the underlying mechanism is unclear. An untargeted lipidomic profiling was therefore performed to gain an insight into the effect of microplastics on a vulnerable coral (Turbinaria mesenterina) of actively reacting to suspended particles. Expending storage lipids on actions such as increasing 20:4-possessing ether membrane lipids and mitochondrial β-oxidation for immunoactivation was observed in coral hosts. A molecular realignment of symbiotic communication was correspondingly observed from symbiotic algae activating anti-inflammatory actions, which employed the 22:6-deriving effects that expended storage lipids as well, by, for example, increasing 22:6-possessing membrane lipids. Symbiotic algae reacting against the heightened host immunity also led to a metabolic compromise that lowered photoprotective capacity. Worryingly, increasing these polyunsaturated membrane lipids potentially sensitize the cells to oxidative stress-induced cell death that was simultaneously indicated by a sphingolipid profile as lipid peroxidation preliminarily increased in coral. Microplastic accumulation thus potentially increase coral susceptibility to environmental factors being able to elevating the oxidative stress, such as light-heat stress. In this manner, microplastic pollution in the ocean would chronically impair coral health, being highlighted by this study.