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Abstract Filtering facepiece respirators (FFRs) provide effective protection against diseases spread through airborne infectious droplets and particles. The widespread use of FFRs during the COVID-19 pandemic has not only led to supply shortages, but the disposal of single-use facemasks also threatens the environment with a new kind of plastic pollution. While limited reuse of filtering facepiece respirators has been permitted as a crisis capacity strategy, there are currently no standard test methods available for decontamination before their repeated use. The decontamination of respirators can compromise the structural and functional integrity by reducing the filtration efficiency and breathability. Digital segmentation of X-ray microcomputed tomography (microCT) scans of the meltblown nonwoven layers of a specific N95 respirator model (Venus-4400) after treatment with one and five cycles of liquid hydrogen peroxide, ultraviolet radiation, moist heat, and aqueous soap solution enabled us to perform filtration simulations of decontaminated respirators. The computed filtration efficiencies for 0.3 µm particles agreed well with experimental measurements, and the distribution of particle penetration depths was correlated with the structural changes resulting from decontamination. The combination of X-ray microCT imaging with numerical simulations thus provides a strategy for quantitative evaluation of the effectiveness of decontamination treatments for a specific respirator model.