The complex and often safety-critical nature of cyber-physical energy systems makes validation a key challenge in facilitating the energy transition, especially when it comes to the testing on system level. Reliable and reproducible validation experiments can be guided by the concept of design of experiments, which is, however, so far not fully adopted by researchers. This paper suggests a structured guideline for design of experiments application within the holistic testing procedure suggested by the European ERIGrid project. In this paper, a general workflow as well as a practical example are provided with the aim to give domain experts a basic understanding of design of experiments compliant testing.Index Terms-Design of experiments, cyber-physical energy systems, holistic testing, research infrastructure.