Two sponge species, Eurypon sp. 2 and Hymeraphia stellifera, survive seasonal anoxia for months at a time. To understand their tolerance mechanisms, we performed RNAseq and differential gene expression analyses on the sponges, their mitochondria and their microbial symbionts under in situ conditions of normoxia, hypoxia, and anoxia. Each sponge species possessed a unique microbiome, but the microbiomes of each species were dominated by a species-specific Thaumarchaeon and a Gammaproteobacterium. The tolerance of some sponges to prolonged anoxia warrants further investigation and could give them an advantage in future oceans following climate change as well as in ancient oceans when oxygen concentrations were lower than at present.