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Isac Rodrigues Comia,1– 3,&ast; Leonardo Manuel,1– 3,&ast; Regina Daniel Miambo,3,4 Awa Abdul Carimo,3,5 Percílio da Floca Manjate,3,5 Ana Edith Maholela,3,6 Lucas Raimundo Banze,2,3 Titos Paulo Buene,2,3 Noémia Nhancupe,2,3 Irina M Sousa,3,7 Constance A Benson,8 Robert T Schooley,9 Jahit Sacarlal,2 Emília Virgínia Noormahomed2,3,9 1Department of Research and Extension, Faculty of Health Sciences, Lúrio University, Nampula, Mozambique; 2Department of Microbiology, Faculty of Medicine, Eduardo Mondlane University, Maputo, Mozambique; 3Mozambique Institute for Health Education and Research (MIHER), Maputo, Mozambique; 4Department of Para-Clinics, Faculty of Veterinary, Eduardo Mondlane University, Maputo, Mozambique; 5Department of Medicine, Eduardo Mondlane University, Maputo, Mozambique; 6Department of Medicine, Maputo Central Hospital, Maputo, Mozambique; 7Department of Biological Sciences, Faculty of Sciences, Eduardo Mondlane University, Maputo, Mozambique; 8Department of Medicine, Division of Infectious Diseases and Global Public Health, University of California, San Diego, CA, USA; 9Department of Medicine, Division of Infectious Diseases, University of California, San Diego, CA, USA&ast;These authors contributed equally to this workCorrespondence: Emília Virgínia Noormahomed, Av. Salvador Allende, 702, Maputo, Mozambique, Tel +258828810907, Fax +25821304684, Email enoormahomed@gmail.comIntroduction: This study aims to determine the baseline seroprevalence of leptospirosis, a zoonotic and neglected disease, in people living with HIV (PWH) in Maputo, Mozambique, and to evaluate the relationship between selected HIV-related factors that might influence risk of coinfection with leptospirosis, such as degree of immunosuppression, as assessed by CD4 cell count, World Health Organization (WHO) HIV/AIDS clinical stage and antiretroviral therapy (ART) intake.Methods: This was a descriptive cross-sectional analysis of 157 PWH, aged over 18 years old, admitted to the Maputo Central Hospital, in Maputo, Mozambique, between March 2020 and October 2021. The study participants were recruited as a convenience sample regardless of the reasons for their admission. We collected sociodemographic and clinical data, including ART and WHO HIV/AIDS clinical stage, and blood for CD4 cell count and detection of Leptospira IgG antibodies using a commercial Kit ab247199 Leptospira IgG ELISA (www.abcam.com/ab247199) with sensitivity and specificity of 100% and 97.3%, respectively. Laboratory testing was performed at the Faculty of Medicine, Eduardo Mondlane University and Laboratory of Clinical Analysis, in Maputo.Results: Participants were aged 18 to 72 years (median age 39 years; SD ± 10.5), the majority were female 100 (63.7%), from urban areas 138 (87.9%), with secondary-level education 80 (51%). The overall seroprevalence of Leptospira IgG antibodies was 40.1%. The median CD4 cell count was 385 cells/μl (02 to 2297; SD ± 378.47). Higher seroprevalence of Leptospira antibodies was found among participants with CD4 cell counts < 250 cells/μl (54.8%), WHO HIV/AIDS stage IV (70.2%) and those on ART (92%), though there were no statistically significant differences between groups with and without Leptospira antibodies.Conclusion: Our study confirmed that Leptospira antibodies are highly prevalent in PWH in Maputo; however, Leptospira infection was not associated with the degree of immunosuppression, WHO HIV/AIDS clinical stage, or the use of ART. Our data support the need for routine screening for leptospirosis in PWH in Mozambique. Future studies are warranted to characterize the incidence and outcomes of symptomatic leptospirosis in this patient population and to identify circulating serovars and species in the country and region, as well as the implicated reservoirs.Keywords: leptospirosis, co-infection Leptospira and HIV, Leptospira IgG, Mozambique