The influence of variables such as; refrigerant amount, chilling and cooling water temperature, throttle valve opening, cooling and chilling water flow rates, on the efficiency (coefficient of performance – COP) of a water to water carbon dioxide heat pump was investigated. Design of experiments was done using design-expert® 6 software for regression analysis. A response surface method known as central cubic design was used to provide optimum results with minimum experiments. Through multiple regression analysis, an empirical equation relating the COP to the variables was derived. Analysis of variance revealed that these regressions are statistically significant at 95% confidence level compounded with a very low standard deviation and a high adequate precision. The close relationship between the predicted COP values and the actual values further proves the worthiness of the empirical equation. It was observed that cooling water temperature had the highest influence followed by the chilling water temperature. Surprisingly, the amount of the refrigerant was third followed by the throttle valve opening. Understandably, chilling water flow rate had the least effect on the COP. Through response surface diagrams, the interactive influence of the variables were also observed. The COP values arrived at varied from 1.545 to 6.914 although if the variables were optimized fully within the scope of this study, a value of up to 11.8 could be achieved. Still, if the variables range is increased further, higher COP could be achieved. Finally, a discussion was done in a bid to explain these results.