Increasing exposure to deoxygenation as a result of climate warming and localised pollution is emerging as an important contributing factor for widespread coral bleaching and mortality. Some corals have been observed to thrive under multiple extreme conditions including very low O2 levels and high temperatures yet the combined effects of heating and deoxygenation on coral bleaching susceptibility remain unknown. Here, we incorporated deoxygenated seawater into short-term heat assays (CBASS) to show that deoxygenation can lower the thermal limit of an Acropora coral species. Data files provided: 'CBASS_deoxy_ref_transcriptome.fasta' contains the reference transcriptome assembled de novo using SOAPdenovo-Trans using non-bleached samples of the CBASS assay (i.e., 30°C and 33°C) and then filtered to keep only reads ≥ 500 bp in length (20,115 contigs). 'CBASS_deoxy_BIS_photos_Initial_and_poststress.pdf' contains images of coral fragments alongside a colour reference chart for estimating bleaching index scores (BIS) before experiment starts (initial) and post 6hr stress phase. Sample IDs are denoted as: H0/HH = normoxia/deoxygenation treatment, 30/33/36/39 = temperature in °C, T1 = time point 1, R1/2/3/4 = replicate 1/2/3/4. 'CBASS_deoxy_SymPortal_output_files.zip' contains all SymPortal (https://symportal.org) output files.