This article aims at presenting the missionary population belonging to the Comboni Missionary Sisters who served in Eritrea between 1914 and 2014 . The choice of this congregation is due to the quality and reliability of available data found in the Comboni Missionary Sisters’ Private Archives (Verona and Asmara); to their weight in terms of number and activities (health, education, social works) carried out in Eritrea; to the possibility of including a gender perspective in the analysis, and applying the ethnodemographic method. Furthermore, the founder Daniele Comboni’s thought about the importance of female missionaries in implementing his idea of “reconstructing Africa through Africans” opened new opportunities for the missionaries themselves. Thus the CMS missionary experience is contextualized in the socio-political and cultural environment in which it took place, underlining the transition from colonial actors to postcolonial subjects. The main challenge of this article is to outline the demographic history of Italian CMS in Eritrea, highlighting their specificities in terms of mobility, age at arrival, mortality and morbidity.