Some wood-destroying fungi are increasingly present in Quebec, Canada and this reported increase seems to coincide with climate change. Serpula lacrymans is a brown rot fungus that is one of the most destructive fungi reported across the province. This research project aims to document and simulate the spread of the biodegradation in wood-frame buildings and, more specifically, to investigate the impact of the presence of the fungus S. lacrymans in wood-based components on the hygrothermal performance of wood-framed wall assemblies. The proposed methodology assesses hygrothermal performance as a function of different envelope assemblies and environmental conditions. Coupled heat and moisture transport is simulated under a variety of outdoor environmental conditions and indoor conditions, for 7 regions in Quebec. The degradation criterion is based on exposure times to humidity and temperature levels conducive to the growth of this fungus. S. lacrymans has a particular ability compared to other decay fungi in that it can move water from its source towards seeking nutrients. Thus, the presence of S. Lacrymans in the envelope assemblies is modeled with two means: modified water transport properties obtained from laboratory measurements on contaminated wood and addition of parallel paths in wood components to simulate moisture transfer in the assemblies. Being able to prevent damage caused by S. Lacrymans could help avoid the demolition of certain buildings, thereby making this built infrastructure more resilient in the face of climate change.