Abstract Sickle cell disease (SCD) is an important cause of death in young children in Africa, which the World Health Organization has declared a public health priority. Although SCD has been studied at the continental scale and at the local scale, a picture of its distribution at the scale of an African country has never been given. The aim of this study is to provide such a picture for the Republic of Gabon, a country where precisely the epidemiology of SCD has been poorly investigated. To this effect, 4,250 blood samples from persons older than 15 were collected between June 2005 and September 2008 in 210 randomly selected villages from the nine administrative provinces of Gabon. Two methods were used to screen Sickle Cell Trait (SCT) carriers: isoelectric focusing (IEF) and high-performance liquid chromatography (HPLC). SCT prevalence in Gabon was 21.1% (895/4249). SCT prevalence was significantly larger for the Bantu population (21.7%, n=860/3959) than for the Pygmy population (12.1%, n=35/290), (p = 0.00013). In addition, the presence of Plasmodium sp was assessed via thick blood examination. Age was positively associated with SCT prevalence (odds-ratio for an increase of 10 years in age = 1.063, p = 0.020). Sex was not associated with SCT prevalence. The study reveals the absence of homozygous sickle-cell patients, and marked differences in SCT prevalence between the Gabonese provinces, and also between population groups (Bantu vs Pygmy). These findings could be used by the public health authorities to allocate medical resources and target prevention campaigns.