Near-isothermal compression is desired to achieve high efficiency in many compressor applications. Low heat transfer characteristic of conventional compressors is a major bottleneck in attaining a near-isothermal compression. A high heat transfer rate is possible with an injection of a large number of water droplets using a spray nozzle inside the compression chamber. In this paper, the effectiveness of spray injection to achieve near-isothermal compression is investigated experimentally in a liquid piston compressor for a compression ratio of about 2.5. Parametric investigations are performed by varying injection pressures of spray from 10 psi (69 kPa) to 70 psi (483 kPa), using different spray nozzle angles (60 degrees, 90 degrees, and 120 degrees), and by changing the stroke time of compression. It is observed that water spray injection is highly effective in abating the air temperature rise during the compression process. The pressure-volume plots indicate a significant reduction in the compression work, and they approach near-isothermal compression with spray at higher injection pressures. The isothermal efficiency of compression consistently increases with an increased injection pressure of spray and reaches up to 95% at the highest injection pressure studied (70 psi). Furthermore, the spray nozzle angle marginally affected the isothermal efficiency with a 1-4% improvement with the use of a 60 degrees nozzle angle over a 120 degrees spray angle at all injection pressures. Also, comparable isothermal efficiencies are observed for compression with different stroke times between 3 and 5 s especially at higher injection pressures which highlight the efficacy of spray injection in attaining a high power-density along with high efficiency. Overall, with an optimized spray design, water spray injection can achieve a highly efficient near-isothermal compression in liquid piston.