Under deep-water high-pressure conditions, the multiphase flow characteristics within separators show significant differences compared to conventional separators. When designing subsea separators, it is crucial to consider the impact of pressure to ensure that the design meets the separation objectives while remaining cost effective. This study enhances the theoretical foundations of subsea separator design by analyzing droplet motion behaviors under high pressure and incorporating these influences into a rational design framework. A horizontal separator was designed and integrated into a laboratory-scale separation system for experimental validation. Through the comprehensive testing of separation efficiencies and process dynamics, it was found that increased pressures resulted in a decrease in oil droplet sizes; at pressures exceeding 6 MPa, droplet diameters were observed to drop below 100 μm. This reduction in droplet size extends the required separation time, necessitating larger separator dimensions at higher operational pressures to maintain adequate separation quality. Numerical simulations complement experimental findings by clarifying the underlying separation mechanisms under high-pressure conditions and offering design recommendations for separators deployed in deep-water environments.