The use of cleanrooms is increasing and the expectation is that this growth will continue in the coming decade. When compared to an average office building, cleanrooms consume large amounts of energy due to their high Air Change Rates (ACRs) and strict air conditioning requirements. Application of Demand Controlled Filtration (DCF) is a means to reduce the (fan) energy demand. The question is whether the air quality is compromised at reduced ACR and overpressure conditions in the non-operational hours of a cleanroom. In a cleanroom mock-up, experiments have been performed to investigate the particle concentration build-up for different cases with DCF, including an extreme case with zero ACR and zero pressure difference. For the DCF conditions and the specific case study, conditions for particle concentration outside the cleanroom, that may still provide high-quality Good Manufacturing Practices (GMP) conditions in the cleanroom, are derived from the results. Furthermore, it assumes DCF application via occupancy sensing, i.e. starting DCF 30 min after the last person left the cleanroom. When applying DCF for a normal workweek (production 08:00–17:00), fan energy savings higher than 70% can be obtained without compromising the air quality requirements under normal circumstances. DCF, in combination with a reduced pressure difference, therefore is regarded as a feasible solution to reduce the energy demand of cleanrooms when the personnel in the cleanroom are the main source of contamination. These results are obtained for the presented case study. Though assuming a conservative approach, confirmation of these outcomes for other cleanrooms is recommended.