Mushrooms represent different species of fungi that can be found anywhere with suitable environmental condition for them to survive in soil. Oyster mushroom (Pleurotus ostreatus) is the second most cultivated mushroom worldwide due to simple cultivation, low cost production technology and high biological efficiency. Ventilation system of an indoor mushroom cultivation house is significant to ensure the removal of metabolic gas such as carbon dioxide, CO2 which produced by the mushrooms. High concentration of carbon dioxide grows oyster mushroom with long stems and small undeveloped caps. Therefore, the ventilation system with good airflow was investigated to ensure good quality of mushroom yielded. In this study, a computational fluid dynamics (CFD) simulation was used to simulate the airflow ventilation system in a 3D indoor mushroom cultivation house model geometry. The speed of fans was examined to determine the effective ventilation system in the geometry. The results indicated that the velocity of fan with speed 3 gave the efficient ventilation system in the model. This is due to the least CO2 concentration accumulated in the model by circulating the most CO2 out of the model. The physical mechanisms of these phenomena were analyzed which can be a basis for predicting the airflow in the real-world operation.