C-Saúde was established in 2020 with the assistance of Vanderbilt University Medical Center (VUMC) and the non-profit organisation Friends in Global Health, LLC (FGH). As of early 2023, VUMC has implemented all of its PEPFAR-funded programmes in Mozambique through FGH. The establishment and growth of C-Saúde was an important pillar in the transition strategy for the implementation of PEPFAR programmes supported by VUMC. In this strategy, the resources used to implement VUMC programmes in Mozambique were gradually transferred from FGH to C-Saúde.

In May 2023, as part of this transition process, C-Saúde began implementing all of PEPFAR’s central support activities in the area of Health Information Systems. In October 2023, C-Saúde began providing technical assistance to the districts of Nicoadala and Derre in Zambézia province, serving 26,488 people on antiretroviral treatment (December 2023).

As of October 2024, C-Saúde was implementing all the activities of the Avante programme in Mozambique with funding from the CDC/PEPFAR through VUMC.

In October 2024, C-Saúde began implementing its first programme directly funded by the CDC/PEPFAR. This programme, called Avante Saúde, aims to support the MISAU and PEPFAR partners in the area of Health Information Systems and to support the province of Zambézia in the process of graduating from PEPFAR-funded activities to the Government of Mozambique.