Background Health information systems (HIS) in most developing countries face many challenges. In view of the recurrent weaknesses in preparedness and response during the management of epidemics, we have examined the organization and functioning of the health information system in Burkina Faso. Methods We conducted a cross-sectional study from January 1, 2020 to March 31, 2020 including a review of HIS documents, key informant interviews and direct observations. The study was conducted at the public primary health care (PHC) and community level of Bama and Soumagou, in the rural health districts of Dande and Tenkodogo. Study participants included community-based health workers (CBHWs) and health workers in the PHC areas, community-based organization animators (CBOAs), CBO monitoring-evaluation officers and members of the District management team (DMT). Results While reporting forms used in all health facilities are standardized, they are not necessarily well understood at community level and at the health centers. Reports prepared by CBHWs are often delayed by the head nurse at the primary health care service. Case definitions of epidemic diseases are not always well understood by community-based health workers and front-line health workers. Conclusion The health information system in Burkina Faso can be improved using simple strategies. There is a need to hold regular training/refresher sessions for agents involved in surveillance and to ensure the development of simplified case definitions for emerging diseases and/or diseases of public health interest for community use. Furthermore, existing epidemic management committees need to be revitalized.