The COVID-19 pandemic has underscored the critical need for effective air filtration systems in healthcare environments to mitigate the spread of viral and bacterial pathogens. This study explores the utilization of copper nanoparticle-coated materials for air filtration, offering both antiviral and antimicrobial properties. Highly uniform spherical copper oxide nanoparticles (~10 nm) were synthesized via a spinning disc reactor and subsequently functionalized with carboxylated ligands to ensure colloidal stability in aqueous solutions. The functionalized copper oxide nanoparticles were applied as antipathogenic coatings on extruded polyethylene and melt-blown polypropylene fibers to assess their efficacy in air filtration applications. Notably, Type IIR medical facemasks incorporating the copper nanoparticle-coated polyethylene fibers demonstrated a >90% reduction in influenza virus and SARS-CoV-2 within 2 h of exposure. Similarly, heating, ventilation, and air conditioning (HVAC) filtration pre- (polyester) and post (polypropylene)-filtration media were functionalised with the copper nanoparticles and exhibited a 99% reduction in various viral and bacterial strains, including SARS-CoV-2, Pseudomonas aeruginosa, Acinetobacter baumannii, Salmonella enterica, and Escherichia coli. In both cases, this mitigates not only the immediate threat from these pathogens but also the risk of biofouling and secondary risk factors. The assessment of leaching properties confirmed that the copper nanoparticle coatings remained intact on the polymeric fiber surfaces without releasing nanoparticles into the solution or airflow. These findings highlight the potential of nanoparticle-coated materials in developing biocompatible and environmentally friendly air filtration systems for healthcare settings, crucial in combating current and future pandemic threats.