Crucian carp (Carassius carassius) overwinter in ice-covered lakes and can survive anoxia for several months at low temperatures. The physiological adaptations allowing this survival are well understood at the whole-organism level, but we know less about the molecular machinery coordinating this adaptation to anoxia and reoxygenation and the possible involvement of epigenetic mechanisms. Due to the profound impact of DNA methylation on regulating gene expression, by directly influencing the accessibility of transcription factors and other regulatory proteins to the DNA, it acts as a switch mechanism and makes investigating it particularly interesting. Past RNA sequencing experiments to analyze the whole brain transcriptome have revealed that many genes are expressed differently in response to anoxia. We suspect that some of these changes in gene transcription during anoxia may be influenced by DNA methylation. Utilizing the next-generation Whole Genome Bisulfite Sequencing (WGBS) method combined with RNA sequencing, we investigated the altered gene activity-environment interaction, providing comprehensive, high-resolution, and quantitative methylation data. Our goal was to determine if genes that are differentially regulated during anoxic conditions are under epigenetic regulation by identifying a correlation between the DNA methylation loci on cytosines and differential RNA expression on the transcriptional level during and after anoxia exposure in the brain. The obtained data elucidates the role of DNA methylation in regulating the response to anoxia and guides us toward uncovering potentially novel molecular players in anoxia tolerance.