The Kyoto protocol binded the developed countries to reduce the greenhouse gas emissions at least by 5% by 2008–2012 in order to tackle global warming and climate change. Some of the measures of the governments to achieve this goal are to promote new buildings construction and to retrofit existing buildings while satisfying low energy criteria. This means improving energy efficiency of buildings and energy systems, developing sustainable building concepts and promoting renewable energy sources. The design of a low energy building requires parametric studies via simulation tools in order to optimize the design of the building envelope and HVAC systems. These studies are often complex and time consuming due to a large number of parameters to consider. Hence, this paper aims to set up a methodology that simplifies parametrical studies during the design process of a low energy building. The methodology is based on the Design of Experiments (DOE) method which is a statistical method widely used in industry to perform parametric studies that reduces the required number of experiments.