Gene expression biomarkers can enable rapid assessment of physiological conditions in situ, providing a valuable tool for reef managers interested in linking organism physiology with large-scale climatic conditions. Here, we assessed the ability of quantitative PCR (qPCR)-based gene expression biomarkers to evaluate (i) the immediate cellular stress response (CSR) of Porites astreoides to incremental thermal stress and (ii) the magnitude of CSR and cellular homeostasis response (CHR) during a natural bleaching event. Expression levels largely scaled with treatment temperature, with the strongest responses occurring in heat-shock proteins. This is the first demonstration of a ‘tiered’ CSR in a coral, where the magnitude of expression change is proportional to stress intensity. Analysis of a natural bleaching event revealed no signature of an acute CSR in normal or bleached corals, indicating that the bleaching stressor(s) had abated by the day of sampling. Another long-term stress CHR-based indicator assay was significantly elevated in bleached corals, although assay values overall were low, suggesting good prospects for recovery. This study represents the first step in linking variation in gene expression biomarkers to stress tolerance and bleaching thresholds in situ by quantifying the severity of ongoing thermal stress and its accumulated long-term impacts.