<p>The growing popularity of delta-8-tetrahydrocannabinol (Δ⁸-THC) products has introduced new analytical and interpretive challenges for forensic toxicology laboratories. While delta-9-tetrahydrocannabinol (Δ⁹-THC) and its metabolites have been extensively characterized in postmortem casework, comparable data for Δ⁸-THC remain scarce. This study presents a validated LC-MS/MS method for the quantitation of Δ⁸-THC, Δ⁹-THC, and their primary metabolites in postmortem blood. Sample preparation employed liquid-liquid extraction using water acidified with 10% acetic acid, followed by extraction with hexane: ethyl acetate (90:10, <i>v/v</i>). The validated method was subsequently applied to a selected subset of authentic postmortem blood samples (<i>n</i> = 107) previously identified to contain Δ⁸- and/or Δ⁹-THC-COOH by GC-MS urine testing. Among these cannabinoid-positive urine cases, 39.3% were positive in blood for both Δ⁸- and Δ⁹-THC and their metabolites, whereas 25.2% and 14.0% were positive for only Δ⁸-THC and Δ⁹-THC-related analytes, respectively. Δ⁸-THC blood concentrations ranged from 1.0 to 90.4 ng/mL, and Δ⁸-THC-COOH concentrations ranged from 5.1 to 1484 ng/mL. Additionally, 11-OH-Δ⁸-THC was measured in 11.2% of cases and consistently co-occurred with Δ⁸-THC and Δ⁸-THC-COOH. These findings provide descriptive postmortem concentration data for Δ⁸-THC and highlight the importance of adequate chromatographic resolution of THC isomers. Importantly, we also underscore the interpretive challenges of polycannabinoid findings in postmortem casework, where detection of Δ⁸-THC, Δ⁹-THC, and/or their metabolites should be interpreted as evidence of cannabinoid exposure, and not as definitive evidence of impairment, intoxication, or contribution to death without additional case context.</p>