Susceptibility to pneumococcal infections in Sj?gren syndrome (SS)―an autoimmune inflammatory disease―patients is not well known, although these patients frequently develop respiratory diseases. The relative risk of developing pneumococcal disease in SS patients versus diabetes mellitus type 2 (DM-2) patients, matched by age, gender, and length of enrolment was studied. From January 1998 to September 2013 the records of Donostia University Hospital were analyzed, which among other patient’s data includes: number and type of hospital admissions and number and type of laboratory determinations. Streptococcus pneumoniae isolates of the same serotype causing recurrent infections were characterized by PFGE. The study comprised 127 patients in the SS group (69 primary and 58 secondary) and 127 in the DM-2 group as control. In 12 SS patients, (9.4%) 22 pneumococcal disease episodes were detected. Two patients (1.6%) with a single episode each one were observed among DM-2 patients, p = 0.01, RR for SS patients 6 (95% CI 1.4 to 26.3). No differences could be demonstrated between the two groups of patients in infections caused by Staphylococcus aureus or Streptococcus agalactiae. Most pneumococcal serotypes in SS patients belonged to the 13-valent (50%) and 23-valent (75%) anti-pneumococcal vaccine. SS patients are associated with and increased risk of suffering from pneumococcal disease. Vaccination should be considered in this group of patients.