This study examines the impact of the COVID-19 pandemic on invasive pneumococcal disease (IPD) in Spain from 2019 to 2023. The research, conducted by a team of experts from various institutions in Spain, characterized all national IPD isolates received at the Spanish Pneumococcal Reference Laboratory during the period. Key findings include: 1. **Pandemic Impact**: In 2020, the first year of the pandemic, there was a general reduction in IPD cases across all age groups, followed by a partial resurgence in children in 2021 but not in adults. By 2022, IPD cases in children had returned to pre-pandemic levels, and partially in adults. In 2023, IPD rates surpassed those of the last pre-pandemic year. 2. **Serotype Trends**: The emergence of serotype 3 became a significant concern, becoming the leading cause of IPD in both pediatric and adult populations over the last two years (2022-2023). Serotype 4 also increased in young adults in the last epidemiological years. 3. **Vaccine Contributions**: The study evaluated the potential coverage of different vaccines (PCV13, PCV15, PCV20, PCV21, PCV24) and the 23-valent polysaccharide vaccine (PPV23) for preventing IPD. Newer vaccines with broader coverage, such as PCV20, were found to prevent up to 34% or 39% more IPD cases compared to PCV13. 4. **Discussion**: The study highlights the importance of continuous epidemiological surveillance of IPD, especially in the context of evolving vaccination programs and public health crises like the COVID-19 pandemic. The findings suggest that while existing vaccines have been effective in reducing IPD, the emergence of non-vaccine serotypes and multidrug-resistant strains warrants ongoing vigilance. The potential of newer vaccines with broader coverage is promising but needs further validation. 5. **Conclusion**: The study underscores the need for ongoing surveillance and the development of new vaccines to address the evolving landscape of IPD in Spain.This study examines the impact of the COVID-19 pandemic on invasive pneumococcal disease (IPD) in Spain from 2019 to 2023. The research, conducted by a team of experts from various institutions in Spain, characterized all national IPD isolates received at the Spanish Pneumococcal Reference Laboratory during the period. Key findings include: 1. **Pandemic Impact**: In 2020, the first year of the pandemic, there was a general reduction in IPD cases across all age groups, followed by a partial resurgence in children in 2021 but not in adults. By 2022, IPD cases in children had returned to pre-pandemic levels, and partially in adults. In 2023, IPD rates surpassed those of the last pre-pandemic year. 2. **Serotype Trends**: The emergence of serotype 3 became a significant concern, becoming the leading cause of IPD in both pediatric and adult populations over the last two years (2022-2023). Serotype 4 also increased in young adults in the last epidemiological years. 3. **Vaccine Contributions**: The study evaluated the potential coverage of different vaccines (PCV13, PCV15, PCV20, PCV21, PCV24) and the 23-valent polysaccharide vaccine (PPV23) for preventing IPD. Newer vaccines with broader coverage, such as PCV20, were found to prevent up to 34% or 39% more IPD cases compared to PCV13. 4. **Discussion**: The study highlights the importance of continuous epidemiological surveillance of IPD, especially in the context of evolving vaccination programs and public health crises like the COVID-19 pandemic. The findings suggest that while existing vaccines have been effective in reducing IPD, the emergence of non-vaccine serotypes and multidrug-resistant strains warrants ongoing vigilance. The potential of newer vaccines with broader coverage is promising but needs further validation. 5. **Conclusion**: The study underscores the need for ongoing surveillance and the development of new vaccines to address the evolving landscape of IPD in Spain.