The aim of this work is to study the influence of two surface modification methods, surface grinding to change the surface roughness (from 240 to 4000 grit) and oxidation (furnace at 703 K for 5 h in air), on antibacterial activity against E. coli K12 of a Cu-based bulk metallic glass composite (BMGC). Variations of roughness obtained through grinding in both as-cast and oxidized samples had a minimal effect on antimicrobial activity. Oxidation in resulted in a multilayered structure with an outer CuO layer, followed by Cu2O layer and other phases at greater depths according to microscopy and energy dispersive X-ray results. This oxidation increased antimicrobial performance despite the CuO layer is poorer in copper than the Cu55Zr40Al5 at. % bulk metallic glass composite substrate. This improvement could be attributed to microstructural differences between the layer and the substrate. The fine needle-shape structure of the crystalline oxide layer may account for the improvement since interphase boundaries could constitute easy diffusion paths for Cu ion release while the shape could trigger mechanosensitive channels that can favour and thus promote the migration of copper ions into the cell. Microscopy of the deposited bacteria revealed limited changes of the outer layer of the cells, with slight changes in morphology for the oxidized samples and this is attributed to the higher copper ion released. Minimum Inhibitory Concentration tests revealed that cell degradation takes place at copper concentrations of 222.4 mg/mL, much higher than measurements of copper ion diffusion in the as-cast samples, suggesting that lysis is not the first step in copper ion toxicity. These studies indicate that Cu55Zr40Al5 bulk metallic glass composite shows promise as an antimicrobial material with tuned performance through surface oxidation.