Introduction: Leptospirosis is a zooanthroponosis caused by spirochete bacteria called leptospire of the genus Leptospira. Objective: To contribute to the knowledge and circulation of the Leptospira germ in humans in the Republic of Guinea. Methods: This prospective and descriptive cross-sectional study lasted 18 months, from June 2019 to December 2020. Results: Of 2346 human blood samples analysed in the laboratory using the enzyme-linked immunosorbent assay (ELISA) for IgG antibodies against leptospirosis, the largest number of samples was taken in Lower Guinea (31.58%), followed by Forest Guinea (27.66%), Middle Guinea (20.97%) and Upper Guinea (19.77%). More samples were taken from females (50.89%) than males (49.10%), for a sex ratio of 1.03 in favour of females. In terms of natural regions, Basse Guinée recorded the highest number of female samples (36.85%). On the other hand, the highest number of male samples was observed in Guinée Forestière with 28.55%. The results of anti-leptospira class G immunoglobulin tests identified the germ in 93 patients, representing a prevalence of 4%. The average age of the patients was 45, with extremes ranging from 10 to 90 years. Of the 93 positive cases, the prevalence of Leptospira infection was highest in subjects aged 31 to 40 (46.23%), followed by individuals in the 41 to 50 age group (18.27%). Prevalence was lower in the 11-20 age group (9.67%), the 51-60 age group (7.52%) and the 61-70 age group (3.22%). No cases of Leptospire infection were recorded in the 0-10, 71-80 and 81-90 age groups. Males accounted for 53.76% of Leptospire infections, compared with 46.23% for females, with a 95% confidence interval (CI) ranging from [13.08-20.82]. Lower Guinea recorded 25.80%, followed by Middle Guinea with 32.25%, Upper Guinea with 20.43% and Forest Guinea with a prevalence of 21.51%. The prevalence of Leptospira infection is higher among women in Middle Guinea (21.50%) than in the other natural regions. We also note that Lower Guinea recorded the highest rate of positivity among males at 18.28% compared with the other regions of Guinea. Farmers are the most affected by infections with 46.23%, followed by veterinarians with 25.80%, health workers with 18.28%, retired people with 4.30% and commercial workers with 3.22% (3/93). Students and workers were the least represented in this study, with 1 case each, representing a prevalence of 1.07%. Conclusion: The results obtained prove that the leptospirosis pathogen does exist in the Republic of Guinea in the entire human population.