This study aimed to develop a robust and sensitive method for measuring plastic particles >700 nm in human whole blood using double-shot pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS). The method was applied to 22 healthy volunteers, and four high-production-volume polymers—polyethylene terephthalate, polyethylene, styrene polymers, and poly(methyl methacrylate)—were identified and quantified for the first time in blood. Polyethylene terephthalate was the most prevalent polymer, followed by polyethylene and styrene polymers. Polypropylene was not detected. The mean concentration of quantifiable plastic particles in blood was 1.6 μg/ml, indicating that plastic particles can be bioavailable in the human bloodstream. This study provides a preliminary assessment of human exposure to plastic particles and highlights the need for further research to understand the potential health risks associated with such exposure.This study aimed to develop a robust and sensitive method for measuring plastic particles >700 nm in human whole blood using double-shot pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS). The method was applied to 22 healthy volunteers, and four high-production-volume polymers—polyethylene terephthalate, polyethylene, styrene polymers, and poly(methyl methacrylate)—were identified and quantified for the first time in blood. Polyethylene terephthalate was the most prevalent polymer, followed by polyethylene and styrene polymers. Polypropylene was not detected. The mean concentration of quantifiable plastic particles in blood was 1.6 μg/ml, indicating that plastic particles can be bioavailable in the human bloodstream. This study provides a preliminary assessment of human exposure to plastic particles and highlights the need for further research to understand the potential health risks associated with such exposure.