We investigated physiological responses including calcification, photosynthesis and alterations to polar metabolites, in the scleractinian coral Stylophora pistillata exposed to different concentrations of polyethylene microplastics. Results showed that at high plastic concentrations (50 particles/mL nominal concentration) the photosynthetic efficiency of photosystem II in the coral symbiont was affected after 4 weeks of exposure. Both moderate and high (5 and 50 particles/mL nominal) concentrations of microplastics caused subtle but significant alterations to metabolite profiles of coral, as determined by Nuclear Magnetic Resonance (NMR) spectroscopy. Specifically, exposed corals were found to have increased levels of phosphorylated sugars and pyrimidine nucleobases that make up nucleotides, scyllo-inositol and a region containing overlapping proline and glutamate signals, compared to control animals. Together with the photo-physiological stress response observed and previously published literature, these findings support the hypothesis that microplastics disrupt host-symbiont signaling and that corals respond to this interference by increasing signaling and chemical support to the symbiotic zooxanthellae algae. These findings are also consistent with increased mucus production in corals exposed to microplastics described in previous studies. Considering the importance of coral reefs to marine ecosystems and their sensitivity to anthropogenic stressors, more research is needed to elucidate coral response mechanisms to microplastics under realistic exposure conditions.