A retrospective study of 208 thalassemia patients over 15 years of age (mean age 45.3 ± 16.0 years; 62% female; 56% splenic dependent; 6% transfused) analyzed severe community-acquired bacterial infections requiring parenteral antibiotics or surgery and having a NEWS score >4. Serious bacterial infection occurred in 43 patients (20.7%), with primary bacteremia (23.2%) being the most common, with Klebsiella pneumoniae (20.9%) and Escherichia coli (13.9%) being the main pathogens. Infection-related mortality reached 9.3%. Significant risk factors were hematocrit <21% (OR=3.15; 95% CI 1.32–7.50; p=0.01), splenectomy >10 years (OR=2.46; 95% CI 1.07–5.69; p=0.035), diabetes mellitus (OR=9.92; 95% CI 1.22–49.12; p=0.03) and hepatic hemochromatosis (OR=3.76; 95% CI 1.64–8.63; p=0.002). Thus, the main predisposing factors were severe anemia, long-term splenectomy, diabetes and iron overload in the liver. The study was conducted at the Department of Hematology, Chiang Mai University from September 2013 to September 2023.