OBJECTIVE Nontyphoidal Salmonella (NTS) is a crucial pathogen in immunocompromised patients, especially those with connective tissue disease (CTD) and corticosteroid or immunosuppressant therapy. The aim of this study is to identify the clinical characteristics and outcomes of patients with CTD and NTS bacteremia, and the clinical variations between systemic lupus erythematosus (SLE) and other CTDs. METHODS During a 15-year study period, from 1994 to 2009, NTS bacteremia patients were reviewed from the database of clinical microbiology laboratory. Medical records were reviewed for clinical information and only patients with underlying CTD were included. RESULTS From 1994 to 2009, there were 299 patients with NTS bacteremia. Forty-six (15.4%) patients had certain connective tissue diseases, and SLE was the major CTD, accounting for 73.9% (34) of 46 patients. In comparison with patients without CTD, the patients with CTD were younger (p<0.0001), had a predominance of female gender (p<0.0001), fewer extra-intestinal focal infections (p=0.011), and a lower mortality rate (p=0.008). Overall, there were four fatal cases, accounting for a mortality rate of 8.7% of those afflicted with CTD. The factors of old age (p<0.006), shock at presentation (p=0.033), acute renal failure (p=0.001), and presence of any extra-intestinal focal infection (p<0.0001) were associated with mortality in the univariate analysis. CONCLUSIONS Nontyphoidal Salmonella bacteremia causes substantial morbidity and mortality in patients with connective tissue disease, especially in the elderly population. The aggressive detection of extra-intestinal infections may be beneficial.