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Abstract Background SARS-CoV-2 infection during pregnancy is known to be associated with poor pregnancy outcomes, including pre-eclampsia (PE), prematurity, perinatal and maternal mortality. Data on the burden of SARS-CoV-2 infection among pregnant women and their offspring in Sub-Saharan Africa is limited. We aimed to estimate SARS-CoV-2 seroprevalence and determine PE biomarkers in Mozambican pregnant women with perinatal loss. Methods A cross-sectional study was conducted among women who had a fetal or an early neonatal death at the Maputo Central Hospital (MCH), Mozambique. Anti-SARS-CoV-2 IgG/IgM were determined in maternal and umbilical cord blood and PE biomarkers (sFlt-1 and PIGF) in maternal blood. SARS-CoV-2 RT-PCR was performed in placenta and fetal lung biopsies from participants found to be SARS-CoV-2 seropositive. Results A total of 100 COVID-19 unvaccinated women were included in the study from March 2021 to April 2022. Total SARS-CoV-2 antibodies were detected in 68 [68%; 95CI (58 – 76)] maternal and 55 [55%; 95CI (54 – 74)] cord blood samples. SARS-CoV-2 IgM was detected in 18 cord blood samples and a positive placental RT-PCR in three of these participants. The proportion of women with moderate to high sFlt-1/PIGF ratio was higher in SARS-CoV-2 seropositive women than in those seronegative (71.2% vs 28.8%, p = 0.339), although the difference was not statistically significant. Conclusions SARS-CoV-2 seroprevalence among Mozambican women with perinatal loss was high during the second pandemic year, and there was evidence of vertical transmission in stillbirths. Findings also suggest that maternal SARS-CoV-2 infection may increase the risk of developing PE.