Objective – To describe the key indicators of the health status of women and children at birth and two months after birth in Guadeloupe and Saint Martin, and to compare them with those recorded in mainland France and in the other overseas departments and regions (DROM). Method – The 2021 ENP survey was conducted nationwide for one week from March 15 to 21, 2021, and for nine weeks in Guadeloupe and Saint Martin from March 15 to May 16, 2021. All births occurring in public and private maternity hospitals and birth centers during the study period were included. Results – In Guadeloupe and Saint Martin, 690 and 93 births, respectively, were recorded in the 2021 ENP-DROM. The survey results show that perinatal health indicators in Guadeloupe remain a cause for concern. The preterm birth rate and the proportion of low-birth-weight babies (<2,500 g) are high (10.2% and 10.8%, respectively). Medical factors known to be associated with preterm birth (obesity, high blood pressure, and preeclampsia) were found at higher rates than in mainland France. Regarding contraception, 23.0% of women in Guadeloupe report never having used a contraceptive method (vs. 11.8% in mainland France). Two months into pregnancy, 71.2% of women report breastfeeding their child (30.1% exclusively and 41.1% mixed, compared to 34.4% and 19.8%, respectively, in mainland France). Furthermore, the data show that the socioeconomic context is more unfavorable: 33.5% of women in Guadeloupe and 30.4% in Saint Martin report a monthly income of less than 1,000 euros (vs. 7.5% in mainland France). Conclusion – The results of the 2021 ENP-DROM highlight that perinatal health indicators are generally poorer in Guadeloupe and Saint Martin than those recorded in mainland France. These data are useful for tailoring health promotion campaigns and prevention messages in the field of perinatal care, and for providing the best possible support to women from pregnancy through the postpartum period.