The development of antibiotic resistance among hospital pathogens has provided a great need for new antimicrobial agents. Zinc oxide nanoparticles (ZnO NPs) in combination with various antibiotics can act as a reducing agent for antibiotic resistance. The aim of this study was to investigate the influence and the mechanism of ZnO NPs on the antimicrobial activity of ciprofloxacin (CP) and ceftazidime (CAZ) against Enterococcus faecalis (E. faecalis) and Acinetobacter baumannii (A. baumannii) bacteria in acidic conditions (pH 5.5). ZnO NPs were synthesised using the solvothermal method and characterised. The MIC90 value of ZnO NPs against A. baumannii was 0.25 mg ml-1 and its highest growth-inhibitory activity was observed at 0.125 mg ml-1 for E. faecalis. The Fourier transform infrared spectroscopy spectra of ZnO NPs treated with antibiotics showed the interaction between ZnO NPs and each of the two antibiotics. ZnO NPs at a sub-inhibitory concentration had no effect on the antibacterial activity of CP and CAZ against E. faecalis and CP against A. baumannii. The action mechanism of ZnO NPs for enhancing the antibacterial efficacy of CAZ against A. baumannii was evaluated. ZnO NPs caused to increase in the antibacterial activity of CAZ against A. baumannii, possibly through the release of Zn2+ and increasing of membrane permeability.