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Objectives This study examined the association of self-reported HIV status with history of oral pre-exposure prophylaxis (PrEP) use among reproductive-age women from Lesotho.Methods This study analysed a sample of 6413 women from the 2023–24 Lesotho Demographic and Health Survey (LDHS) data. The data were collected between November 2023 and February 2024. Categorical data were analysed with percentages and χ 2 tests. In addition, ever use of oral PrEP and covariates of self-reported HIV infection were investigated using binary multivariable multilevel logistic regression. HIV infection data were self-reported by the women based on their most recent HIV test.Results The weighted prevalence of self-reported HIV infection among women was 22.1% (95% CI 20.6% to 23.7%). Among women who ever used oral PrEP, the prevalence of self-reported HIV infection was 13.4% (95% CI 9.9% to 17.9%), but was 24.0% (22.0% to 26.1%) among women who have never used. History of oral PrEP use was associated with 62.0% reduction in the odds of self-reported HIV infection (adjusted OR (aOR) 0.38; 95% CI 0.28 to 0.51). Respondents who have heard of a sexually transmitted infection (STI) have 27.0% reduction in the odds of self-reported HIV infection when compared with those who have not heard of an STI (aOR 0.73; 95% CI 0.59 to 0.90). Women aged 25+ years at first sex had 60.0% reduction in the odds of self-reported HIV infection, when compared with those <18 years at first sex (aOR 0.40; 95% CI 0.19 to 0.84). Women with multiple total lifetime number of sexual partners had higher odds of self-reported HIV infection, when compared with those with single lifetime number of sexual partner.Conclusions HIV infection among women in Lesotho remains high. Having a history of oral PrEP use was associated with lower odds of self-reported HIV infection. Stakeholders in healthcare should promote oral PrEP interventions and design programmes for HIV prevention among women.