Coral skeletal Sr/Ca is a palaeothermometer commonly used to produce high resolution seasonal sea surface temperature (SST) records and to investigate the amplitude and frequency of ENSO and interdecadal climate events. The proxy relationship is typically calibrated by matching seasonal SST and skeletal Sr/Ca maxima and minima in modern corals. Applying these calibrations to fossil corals assumes that the temperature sensitivity of skeletal Sr/Ca is conserved, despite substantial changes in seawater carbonate chemistry between the modern and glacial ocean. We present Sr/Ca analyses of 3 genotypes of massive Porites spp. corals (the genus most commonly used for palaeoclimate reconstruction), cultured under seawater pCO₂ reflecting modern, future (year 2100) and last glacial maximum (LGM) conditions. Skeletal Sr/Ca is indistinguishable between duplicate colonies of the same genotype cultured under the same conditions, but varies significantly in response to seawater pCO₂ in two genotypes of Porites lutea, whilst Porites murrayensis is unaffected. Within P. lutea, the response is not systematic: skeletal Sr/Ca increases significantly (by 2-4%) at high seawater pCO₂ relative to modern in both genotypes, and also increases significantly (by 4%) at low seawater pCO₂ in one genotype. This magnitude of variation equates to errors in reconstructed SST of up to -5°C.