Introduction. Invasive meningococcal infections are monitored by the Mayotte Department of Health and Social Affairs (DAS). Method. This analysis is based on data archived at the DAS for the period 2001–2006: case reports, laboratory confirmations, and intervention records. The reference population is that of the 2002 census. Results. The number of cases for the period was 62. The annual incidence was 5.0/10,000 in 2001; 3.1/10,000 in 2002; 13.1/10,000 in 2003; 5.0/10,000 in 2004; 8.7/10,000 in 2005; and 3.8/10,000 in 2006, much higher than that observed in France, in the French departments of the Americas (DFA), or on the island of Réunion. The incidence rate before the age of 1 year is 57/105. The outcome was favorable in 93% of the 57 documented cases, and the case fatality rate was 7%. The majority of cases originated from two municipalities (p<0.0001) and neighborhoods with a high migrant population. Of the serogrouped strains (n=57), 70% were serogroup B and 26% were serogroup W135. The phenotypes B:4:P1-4, B:NT:P1-4, and W:2a:P1-2,5 accounted for 43%, 22.2%, and 20% of the phenotyped strains, respectively. The incidence of the W:2a:P1-2,5 strain has decreased since 2003. Discussion. Population density and age structure are contributing factors. The strains circulating in Mayotte appear to be of moderate virulence and of a different nature than those circulating in the Comoros.