Carbon monoxide (CO) toxicity associated with exposure to an environmental, exogenous source, is routinely investigated in the field of forensics. Paramedics responded to the home of a 60-year-old woman who complained of persistent nausea, dizziness, and fatigue. Her initial carboxyhemoglobin (COHb) saturation was 25% as measured by paramedics in the field via pulse CO-oximetry (SpCO) and was, 2 hours later, confirmed by hospital laboratory spectrophotometric analysis to be 16% after initial treatment in the emergency department. The clinical presentation of environmental CO exposure and subsequent death notification to the North Carolina Office of the Chief Medical Examiner prompted an extensive investigation into the suspected residential source of CO, which ultimately ruled out all exogenous sources. The medicolegal death investigator later discovered an updated hematology consultation note, which determined the actual source of the CO to be endogenously produced from disease. Herein, we report an unusual fatality involving enhanced endogenous CO production caused by warm autoimmune hemolytic anemia. This unique case report and brief literature review of disease-related elevation of endogenous CO will shed light on this lesser-known phenomenon alerting the forensic community to its potential occurrence and need for consideration when sources of environmental exposure have been exhausted. K E Y W O R D Scarbon monoxide toxicity, carboxyhemoglobin, endogenous carbon monoxide, forensic pathology, medicolegal death investigation, warm autoimmune hemolytic anemia Highlights• Endogenous carbon monoxide (CO) production can reach clinically measurable levels in the setting of hemolytic anemia.• Endogenous CO may mimic symptoms of an environmental exposure in forensic investigations.• Among cases of warm autoimmune hemolytic anemia, those mediated by complement component 3 (C3) can sometimes be fatal.