BACKGROUND: The United States Advisory Committee on Immunization Practices recommends administration of the 13-valent pneumococcal conjugate vaccine in series with the 23-valent pneumococcal polysaccharide vaccine for prevention of pneumonia in the elderly. Reports of autoimmune or auto-inflammatory diseases as a result of pneumococcal vaccination, especially pneumococcal conjugate vaccine, are extremely rare. CASE PRESENTATION: We present a case of severe serositis in a 75-year-old Caucasian woman complicated by pericardial and pleural effusions in the setting of recent 13-valent pneumococcal conjugate vaccine vaccination and no other obvious etiology. Our patient required steroid treatment, thoracentesis, chest tube, and pericardial window and subsequently recovered to her baseline. CONCLUSIONS: To the best of our knowledge, no such reaction to the 13-valent pneumococcal conjugate vaccine has previously been documented. Although the benefits of vaccination outweigh the risks, knowledge of this potential side effect can help clinicians in diagnosis and treatment of similar patients.