Objective – To describe the key indicators of the health status of mothers and newborns at birth in Mayotte in 2021, track changes since 2016, and compare the situation with that of mainland France. Special attention was given to mothers’ social security coverage in Mayotte, as this is a significant issue for the territory. Methods – The ENP-DROM enabled the fieldwork for the 2021 National Perinatal Survey (ENP) to be extended to the overseas territories. In Mayotte, the survey lasted six consecutive weeks (October 25–December 5), compared to one week in mainland France. All births occurring in private and public maternity hospitals and birthing centers were included. Results – A total of 991 live births (involving 982 mothers) were included in Mayotte. The survey shows that while the proportion of mothers in highly precarious situations in Mayotte is lower than in 2016, the situation remains a cause for concern. Monthly household income is less than €500 for 43.5% of women (compared to 57.0% in 2016 and 1.9% in mainland France), and 33.3% have an educational level below middle school (compared to 45.0% in 2016 and 1.7% in mainland France). The average maternal age (28 years), the migration context (74.1% of women were born abroad), and the proportion of women without health insurance (59.2%) have not changed since 2016. In Mayotte, 39.6% of women have never used contraception (compared to 33.4% in 2016 and 11.8% in mainland France). The rate of preterm births (9.9%) and low-birth-weight newborns (