The opioid epidemic, fueled by increased use of opioids like fentanyl, claims close to 50,000 deaths annually, out of about ten million users. However, the genetic aspects of fentanyl consumption are relatively understudied and a greater understanding of genetic biomarkers of fentanyl usage would be immensely beneficial to the public health system. This study aimed to analyze post-mortem brain tissue samples of fentanyl-using subjects and healthy controls to identify biomarkers of fentanyl use. 186 differentially expressed genes were selected and entered into a protein interaction network, following which commonly present functions and pathways were analyzed. Processes including inflammatory response and responses to the metabolic process were identified as potential biomarkers. This study highlighted the connections between opioid use and the immune system, an emerging area of study.