A novel core-shell silica based antimicrobial nanoparticle was synthesized. The Stöber silica shell has been engineered to accommodate copper. Synthesis of the core-shell Cu-silica nanoparticle (C-S CuSiNP) involves preparation of base-hydrolyzed Stöber silica “seed” particles first, followed by the acid-catalyzed seeded growth of the Cu-silica shell layer around the core. Scanning electron microscopy and transmission electron microscopy showed monodispersed, spherical shaped nanoparticles with smooth surface morphology. Characterization of particle size distribution in solution by the Dynamic Light Scattering (DLS) technique was fairly consistent with the electron microscopy results. Loading of Cu to nanoparticles was confirmed by the SEM-Energy Dispersive X-Ray Spectroscopy (EDS) and Atomic Absorption Spectroscopy (AAS). Antibacterial efficacy of C-S CuSiNP was evaluated against E.coli and B.subtilis using Cu hydroxide (“Insoluble” Cu compound) and copper sulfate as positive control and silica “seed” particles (without Cu loading) as negative control. Minimum Inhibitory Concentration (MIC) of C-S CuSiNP was evaluated by measuring the fluorescent intensity of resorufin to determine the decrease in viable cells with increase in copper concentration in C-S CuSiNP. The MIC value of C-S CuSiNP against both E.coli and B.subtilis was estimated to be 4.9 ppm. Bac-light fluorescence microscopy based assay was used to count relative population of the live and dead bacteria cells. Antibacterial study clearly shows that C-S CuSiNP is more effective than insoluble Cu hydroxide particles and copper sulfate at equivalent metallic Cu concentration, suggesting more soluble Cu in C-S CuSiNP material due to its coreshell design.