Combined ocean acidification and hypoxia (OAH) is becoming increasingly widespread and severe along the California coast due to anthropogenic carbon dioxide emissions exacerbating upwelling. The transcriptomic response of the larval red sea urchin Mesocentrotus franciscanus to OAH was assessed to determine the physiological consequences of OAH stress. Analysis of this transcriptome reveals a graded response proportional to OAH severity in addition to select pH and DO breakpoints that impact morphology and gene expression. By assessing the physiological response and gene expression of these species, we can inform future management actions to mitigate OAH-related impacts and maintain fishery populations.