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Background: Identifying patients at higher risk of postoperative sepsis (PS) may help to prevent this life-threatening complication., Objectives: This study aimed to identify the rate and predictors of PS after primary bariatric surgery., Setting: An analysis of the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) 2015-2017., Methods: Patients undergoing elective sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) were included. Exclusion criteria were revisional, endoscopic, and uncommon, or investigational procedures. Patients were stratified by the presence or absence of organ/space surgical site infection (OS-SSI), and patients who developed sepsis were compared with patients who did not develop sepsis in each cohort. Logistic regression was used to identify independent predictors of PS., Results: In total, 438,752 patients were included (79.4% female, mean age 44.6±12 years). Of those, 661 patients (.2%) developed PS of which 245 (37.1%) developed septic shock. Out of 892 patients with organ/space surgical site infections (OS-SSI), 298 (45.1%) developed sepsis (P <.001). Patients who developed PS had higher mortality (8.8% versus .1%, P < .001), and this was highest in patients without OS-SSI (11.8% versus 5%, P = .002). The main infectious complications associated with PS in patients without OS-SSI were pneumonia and urinary tract infection. Independent predictors of PS in OS-SSI included RYGB versus SG (OR, 1.8), and age ≥50 years (OR, 1.4). Independent predictors of PS in patients without OS-SSI were conversion to other approaches (OR, 6), operation length >2 hours (OR, 5.7), preoperative dialysis (OR, 4.1), preoperative therapeutic anticoagulation (OR, 2.8), limited ambulation most or all of the time (OR, 2.4), preoperative venous stasis (OR, 2.4), previous nonbariatric foregut surgery (OR, 2), RYGB versus SG (OR, 2), hypertension on medication (OR, 1.5), body mass index ≥50 kg/m 2 (OR, 1.4), age ≥50 years (OR, 1.3), obstructive sleep apnea (OR, 1.3)., Conclusion: Development of OS-SSI after primary bariatric surgery is associated with sepsis and increased 30-day mortality. Patients without OS-SSI who develop PS have a significantly higher mortality rate compared with patients with OS-SSI who develop PS. Early identification and intervention in patients with PS, including those without OS-SSI, may improve survival in this high-risk group., (Copyright © 2020 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)