Enhancing the performance of traditional vapor compression cooling cycles is an important aspect in the quest to minimize global energy consumption, to own sustainable energy systems soon, and to preserve the environment. This study performed a comparative analysis of the performance of a water cooler with different working fluids to replace R143a and improve system performance. A mathematical model derived from energy and exergy analysis is developed for the evaluation of the effect of operating conditions on the system COP, exergetic losses, and exergetic efficiency. The evaluation has been conducted for evaporation and condensation temperatures ranging between -30°C to 15°C and 25°C to 55°C, respectively. Results showed that the cycle with R510A has the maximum COP. The average system COP with R510A, RE170, and R152a are 19.54%, 13.53%, and 9.36 % higher than that with R134a, respectively. The highest value of exergy loss takes place in the compressor. At different working fluids, exergy losses decrease as evaporation temperatures increase and condensation temperatures decrease. The system with R510A has the minimum exergy losses. The average exergy losses for systems with R510A, RE170, and R152a are 34.62%, 28.33%, and 18.64% lower than that of R134a, respectively. The system with R510A has higher exergy efficiency and R134a has the minimum values of exergy efficiency. Generally, the water cooler provided better performance with R510A and RE170 than with R152a and R134a. Therefore, R510A can be considered as the best replacement for R134a and R152a.