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Introduction: Oral squamous cell carcinoma (OSCC) is one of the highest-ranking cancers among both genders in Pakistan. Obesity is linked to a much higher risk for developing multiple cancer types. Individuals with Diabetes mellitus (DM) face an increased risk for developing oral cancer. Hence, the objective of this study was to identify the effect of obesity and DM on the prognosis of OSCC patients. Methods: This retrospective cohort analysis was conducted on 386 patients diagnosed and treated for OSCC at The Aga Khan University Hospital, Karachi, Pakistan. Patient information was obtained from hospital medical records. Obesity was defined as having a body mass index (BMI) of ⩾25 kg/m2 according to the WHO Asian cut-offs for BMI. Patient BMI was correlated with diabetes status, clinicopathological features and overall survival. Kaplan-Meier survival analysis was performed, along with univariate and multivariate cox regression analysis to test the effect of obesity and diabetes on overall survival. Results: In a set of 386 patients, there were 296 males (76.7%) and 90 females (23.3%). The mean BMI was 24.4 (SD ± 5.25) and 42.7% of patients were found to be obese (⩾25 BMI). 64 patients (16.6%) were diabetic. The risk of death was significantly higher in underweight patients (P =.035) compared with normal weight individuals. Diabetics had a higher mean BMI compared with non-diabetics. However, DM was not a statistically valid predictor of survival. Conclusion: Underweight OSCC patients were at a higher risk of death compared with normal weight OSCC patients. [ABSTRACT FROM AUTHOR]