Background <p>Pneumococcal disease (PD) represents a significant public health concern, impacting healthcare systems across Latin America. Mexico’s National Immunization Program introduced infant vaccination with the 7‑valent pneumococcal conjugate vaccine (PCV7) in 2008, switching to the 13‑valent pneumococcal conjugate vaccine (PCV13) in 2011. Adult vaccination has been included since 2004. Data on Mexico’s disease burden remain limited; therefore, this study aimed to estimate the burden of clinical syndromes associated with pneumococcal disease in 2019.</p> Methods <p>We conducted a retrospective analysis using Mexican administrative hospitalization and mortality databases. Clinical syndromes—including pneumonia, bacteremia, meningitis, and other invasive diseases—were identified using International Classification of Diseases, Tenth Edition (ICD-10) codes. For each syndrome, hospitalization rates, case fatality rates (CFR), and mortality rates were calculated by age group (&lt; 1, 1–4, 5–17, 18–49, 50–59, and ≥ 60 years).</p> Results <p>In 2019, 119,628 hospitalizations related to these syndromes were reported, with pneumonia accounting for 78% of cases. Hospitalization rates were highest among infants aged &lt; 1 year, at 557 per 100,000. CFRs increased with age, reaching 27.8% for pneumonia and 70.9% for bacteremia in adults aged ≥ 60 years. Mortality rates were highest for pneumonia in older adults (156.3 per 100,000) and infants aged &lt; 1 year (45.2 per 100,000).</p> Conclusions <p>These findings highlight the persistent burden of clinical syndromes associated with PD in Mexico despite vaccination efforts, emphasizing the need for improved immunization strategies, particularly among older adults, and strengthened surveillance to inform public health policies.</p> Clinical trial number <p>Not applicable.</p>