Global warming has triggered an increase in both prevalence and severity of coral disease outbreaks, yet little is known about the mechanism(s) by which coral disease functions, or what controls a corals’ susceptibility to infection. Failure to address such fundamental questions limits our ability to develop remediation strategies for diseased corals. Here, we track infection dynamics and metabolic interactions at the levels of the tissue and single cells, with the goal of understanding the exchanges that occur between Pocillopora damicornis and Vibrio coralliilyticus under thermal stress. Inoculations were performed in light and dark conditions using the “Coral-on-a-Chip” microfluidic system. Infected corals inoculated with 15N-labeled, DsRed-tagged V. coralliilyticus were paired with non-infected, control corals and both were exposed to isotopically H13CO3--labeled seawater. The progression of the infection was monitored in real time, and once clear symptoms of disease (the development of lesions, biofilms and/or tissue necrosis) were observed, the experiment was quenched and the samples fixed. Subsequent NanoSIMS imaging enabled us to track the 15N-labeled pathogens in coral tissue and the assimilation and turnover of photosynthetically-fixed H13CO3- in the symbiont dinoflagellates. We present high-resolution images of the infection process, from the initial innoculation of the coral to the colonization of tissue and the development of disease symptoms to the reduction in photosynthetic performance of the symbiont dinoflagellates that accompanies the progression of infection. Our results add a unique mechanistic perspective to the complexities of coral disease, which is crucial for understanding how corals will fare under global climate change.