Objective. To study the incidence, time-trends and outcomes of serious infections in Sjögren's syndrome (SS). Methods. We examined the epidemiology, time-trends and outcomes of five serious infections (opportunistic infec-tions (OI), skin and soft tissue infections (SSTI), urinary tract infection (UTI), pneumonia, and sepsis/bacteraemia) in hospitalised patients with SS, using the 1998-2016 U.S. National Inpatient Sample. Multivariable-adjusted logistic regression analyses analysed the association of patient, comorbidity and hospital characteristics with healthcare utilisation (hospital charges, length of hospital stay, discharge to non-home setting), and in-hospital mortality. Results. We found 49,897,331 hospitalisations with serious infections in general population and 69,239 in patients with SS. Compared to serious infections hospitalisations in people without SS, SS patients were older, and more likely to be female, white or have Deyo-Charlson index score ≥2. Serious infections during the study period 1998-2016 were: OI, 3%; SSTI, 19%; UTI, 6%; pneumonia, 37%; and sepsis, 34%. Serious infection rates/100,000 NIS hospitalisations increased from 1998-2000 to 2015-2016: OI, 0.16 to 0.46; SSTI, 0.55 to 2.90; UTI, 0.25 to 1.96; pneumonia, 2.78 to 5.43; sepsis, 0.63 to 10.71. In multivariable-adjusted analyses, older age, Deyo- Charlson index score ≥2 and medium or large hospital bed size were associated with higher healthcare utilisation and in-hospital mortality. Medicare insurance, Northeast region, non-rural hospital were associated with higher healthcare utilisation outcomes only. Conclusion. We quantified the increasing disease burden of serious infections in people with SS, and described its epidemiology. Association of factors with serious infection hospitalisation outcomes identifies potential targets for future interventions.