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Invasive meningococcal disease (IMD) is a devastating disease with significant mortality and long-term morbidity. The COVID-19 pandemic and containment measures have affected the epidemiology of infectious pathogens. This study’s aim was to assess IMD trends in Israel prior to and during the COVID-19 pandemic. The <i>Neisseria meningitidis</i> invasive infection is a notifiable disease in Israel. Laboratory analysis includes serogrouping and molecular characterization. The overall national IMD incidence rate (1998–2022) was 0.8/100,000 population. The IMD incidence rates declined during the pandemic years (0.3/100,000 in 2020–2022 vs. 0.9/100,000 in 1998–2019). The number of notified IMD cases declined by 65% in 2020–2022. The case fatality rate among laboratory-confirmed IMD cases was 9% (47/521, 2007–2022). Mortality risk markers included cases’ age (older) and socio-economic status (lower). Overall, most <i>Neisseria meningitidis</i> isolates were of serogroup B (62.6%), and the most prevalent clonal complex (CC) was CC32 (24.2%). Serogroup B prevailed in cases aged 0–9 years (74.5%) and less in cases aged 10 years and above (39%). <i>Neisseria meningitidis</i> serogroups and CC distribution altered recently with a decline in serogroup B fraction, an increase in serogroup Y, and a decline in CC32. Ongoing IMD surveillance is necessary to assess trends in circulating strains and support decision-making on meningococcal vaccination programs.