Nosocomial infections are among the major public health concerns, especially during the ongoing Covid19 pandemic. There is a great demand for novel chemical agents that are capable of killing specific pathogens or augmenting the efficiency of existing disinfectants. Herein, we report the synthesis and comprehensive characterization (through FT-IR, HR-MS, SEM, TGA-DSC, CV, UV and SCXRD analyses) of six novel copper(ii) complexes, [CuL(4X-An)] (5a-5d), [CuL(An)] (5e), and [CuL(benzhydrylamine)] (5f), and their evaluation as anti-microbial agents against WHO priority pathogens, confirming their possible use in hospital settings. The compounds were synthesized with a Schiff base (H2L) obtained by the condensation reaction of 3-acetyl-6-methyl-2H-pyran-2,4(3H)-dione (DHA) and benzohydrazide and further addition of differentp-substituted aniline (An) molecules. Single crystal structure analyses revealed that the aniline derivatives are isostructural to the copper atom in a square planar coordination, while the benzhydrylamine complex forms a dimer (5f), with a square pyramidal coordination geometry for the metal. Time-kill kinetics and reduced microbial recovery studies revealed excellent bactericidal action againstStaphylococcus aureusandEnterococcus faecalis. Particularly, the novel compound5fsignificantly reduced microbial recovery compared to ethanol-based sanitisers. In fact, addition of5fto 70% ethanol remarkably synergized the killing with >6-log reduction in microbial burden. Overall, our novel compounds would increase the disinfection efficacy in hospitals and industries, thereby improving the efficiency and minimizing the risk of infections.