FLASH radiotherapy delivers therapeutic doses at ultra-high dose rates and may reduce normal tissue injury while preserving tumor control, but its mechanisms remain unclear. Radiolytic oxygen depletion has been proposed as one contributor, yet the combined effects of initial oxygen conditions and the spatial distribution of protons on oxygen depletion remain insufficiently understood. Geant4-DNA was used to simulate water radiolysis induced by 100 MeV protons in oxygenated water. All primary protons were introduced simultaneously, representing an idealized limiting case of zero pulse duration. Initial dissolved oxygen concentration and source radius were varied to evaluate oxygen depletion coefficients and the temporal evolution of chemical species. Relative changes in oxygen enhancement ratio were estimated using the Grimes model. Oxygen depletion coefficients increased with initial dissolved oxygen concentration, whereas reducing the source radius and increasing proton spatial aggregation decreased net oxygen depletion per unit dose. Species evolution supported enhanced radical recombination or termination at the smaller source radius and competition with oxygen scavenging pathways. The relative change in OER was jointly determined by initial oxygen conditions, oxygen depletion coefficients, and absorbed dose, with greater sensitivity under hypoxic conditions. These findings show that initial oxygen conditions and proton spatial distribution jointly regulate microsecond-scale oxygen depletion and the associated relative change in OER.