Background: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Information on the prevalence of SARS-CoV-2 antibodies in women and children in Madinah has been limited. The current study aimed to evaluate SARS-CoV-2 IgG seropositivity among women and children at Madinah Maternity and Children’s Hospital. Methods: In this cross-sectional study, 579 participants were recruited between January and April 2021 from Madinah Maternity and Children’s Hospital, Saudi Arabia. Data concerning age, sex (for children), blood group, and height and weight (for women) were collected from the hospital database. SARS-CoV-2 anti-spike (anti-S) IgG antibodies were detected by enzyme-linked immunosorbent assay (ELISA). Results: Over 58% of children (n = 195), including 60% of children ≤1 year (n = 75), and 50.2% (n = 124) of women were SARS-CoV-2 anti-S IgG seropositive. Significantly higher anti-S IgG levels were observed in children than in women (0.78 ± 1.05 vs. 0.65 ± 0.98, p = 0.008). Compared with women, children had higher odds of high SARS-CoV-2 anti-S IgG levels (odds ratio: 1.41; 95% confidence interval: 1.01–1.97; p = 0.041). No significant associations were observed for anti-S IgG levels with age in women or children or with body mass index among women. Conclusion: Non-reported COVID-19 infections were more prevalent among children than women, and non-reported COVID-19 infections children represent a viral transmission risk; therefore, increased screening, especially among school-aged children, may represent an important COVID-19 preventive control measure.