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Objective: It is unclear whether pre-COVID medical conditions are risk factors for post-COVID major depressive episode (MDE). We aimed to determine which pre-COVID medical conditions are risk factors for post-COVID MDE after a hospitalization for COVID-19., Methods: We conducted a nested retrospective case-cohort study within a cohort of 650 patients evaluated six months after hospitalization for COVID-19 at Bicêtre hospital, France. Nine medical conditions present before COVID-19 (High blood pressure, obesity, type 2 diabetes, cardiac, respiratory and renal disease, immune deficiency, neoplasia and liver disease) were extracted from medical records. MDE was assessed using the Structured Clinical Interview for DSM-5 Disorders-Clinician Version (SCID-5-CV). Bivariate and multivariable analyses were performed to determine which pre-COVID medical conditions are independent risk factors for post-COVID new-onset MDE., Results: Patients mean age was 62.8 (15.8), 258 (39.7 %) were women; 301 (46.3 %) had high blood pressure, 205 (32.4 %) had obesity, and 186 (28.6 %) had type 2 diabetes. Thirty-six (5.5 %) patients were diagnosed with a new-onset MDE. In contrast to other medical conditions, type 2 diabetes was significantly associated with new-onset MDE (OR = 2.51 [1.19-5.29])., Conclusion: Unlike other pre-COVID medical conditions, type 2 diabetes is a risk factor for post-COVID MDE. Patients with type 2 diabetes should be screened for MDE after a hospitalization for COVID-19., Competing Interests: Declaration of competing interest All authors have completed the ICMJE uniform disclosure form at http://www.icmje.org/disclosure-of-interest/ and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work. Dr. Montani reported personal fees from Actelion, GSK, Pfizer, MSD, Chiesi, Boehringer, and Incyte Biosciences France, grants from Bayer and MSD, and nonfinancial support from Acceleron outside the submitted work. Dr. Monnet reported personal fees from Getinge Pulsion Medical and Baxter outside the submitted work. Dr. Becquemont reported grants from Sanofi Genzyme for a presentation concerning Gaucher disease, and pharmacogenetics and drug interactions with Eliglustat outside the submitted work. No other disclosures were reported., (Copyright © 2024 Elsevier Inc. All rights reserved.)