Sickle cell disease (SCD) is a genetic disorder caused by a mutation in the beta hemoglobin gene, resulting in red blood cell distortion, hemolysis, and severe pain episodes. Chronic pain in SCD is believed to be largely driven by neuroinflammation and central sensitization, yet the exact neurobiological mechanisms remain unclear. Hemorphins, opioid peptides derived from beta-hemoglobin, may bridge this gap by influencing opioid signaling pathways that could alleviate the pain experienced in SCD. In this study, we investigated the levels of hemorphins in both plasma and brain tissues of transgenic SCD mice using liquid chromatography-mass spectrometry (LC-MS).