The internal relative humidity (RH) plays a crucial role in most of the concrete properties. Self-desiccation caused by continuous cement hydration is a major factor affecting the RH of concrete. This paper investigates the relationship between RH and microstructure for cementitious systems in the case of self-desiccation. A series of paste specimens prepared with different binder and water-binder-ratio (w/b) were cured under sealed conditions from 1 day to 1.5 years. The RH and microstructure of the paste specimens were measured. The microstructure characteristics under study include porosity, pore size, evaporable and non-evaporable water content. The results reveal that the RH of cementitious system drops to a great extent in the first 105 days' hydration and decreases slowly afterwards. The blended materials such as fly ash, slag or limestone powder have different influences on the RH. A mathematical model between RH and the average pore diameter is proposed for cementitious systems under self-desiccation, regardless of age, w/b or cement type.