Population exposure to persistent organic pollutants (POPs) may result in detrimental health effects, especially to pregnant women, developing foetuses and young children. We are reporting the findings of a cross-sectional study of 605 mothers in their late pregnancy, recruited between August 2020 and July 2021 in southern Malawi, and their offspring. The aim was to measure the concentrations of selected POPs in their maternal serum and indicate associations with social demographic characteristics and birth outcomes. A high level of education was the main predictor of p,p′-DDE (p = 0.008), p,p′-DDT (p < 0.001), cis-NC (p = 0.014), o,p′-DDT (p = 0.019) and o,p′-DDE (p = 0.019) concentrations in maternal serum. Multiparity was negatively associated with o,p′-DDE (p = 0.021) concentrations. Maternal age was also positively associated (p,p′-DDE (p = 0.013), o,p′-DDT (p = 0.017) and o,p′-DDE (p = 0.045) concentrations. Living in rural areas was inversely associated with high maternal serum concentrations of p,p′-DDT (p < 0.001). Gestational age was positively associated with p,p′-DDE (p = 0.031), p,p′-DDT (p = 0.010) and o,p′-DDT (p = 0.022) concentrations. Lastly, an inverse association was observed between head circumference and t-NC (p = 0.044), Oxychlordane (p = 0.01) and cis-NC (p = 0.048). These results highlight the need to continue monitoring levels of POPs among vulnerable populations in the southern hemisphere.