The aim of this study was to evaluate the association between overweight and severity, drug response, and clinical outcomes of novel coronavirus disease 2019 (COVID-19).In this retrospective cohort study, we reviewed medical records of 240 COVID-19 patients admitted to Union Hospital in Wuhan, China, between December 24, 2019, and March 25, 2020. Physical, clinical, laboratory, radiological characteristics, treatment, and outcome data were abstracted. Patients who were obese [body mass index (BMI) ≥28 kg/m], underweight (BMI < 18.5 kg/m), under 18 years old, pregnant, or still in hospital were excluded. Disease severity was classified as moderate or severe pneumonia based on the World Health Organization interim guidance. Overweight was defined as BMI ≥24 kg/m and <28 kg/m. Patients were followed for discharge or death through April 10, 2020. We used logistic regression models to identify risk factors for severe disease, Cox proportional hazard models to explore associations between medications and patient outcomes (discharge or in-hospital death), and Kaplan-Meier survival curves and Cox regression models to evaluate risk factors for in-hospital death.One-half of patients (120, 50.0%) had severe pneumonia, while nearly one-half (114, 47.5%) were overweight. Among patients over 45 years old, overweight patients had significantly lower rates of fatigue, higher rates of headache, and higher median C-reactive protein levels. Patients under 45 years old had higher rates of cough and myalgia and higher proportions of increased alanine aminotransferase and lactic dehydrogenase, as well as more pulmonary lobes involved in the pneumonia revealed by chest computed tomography scans. Overweight patients were at higher risk of developing severe pneumonia. Although weight was not a risk factor for in-hospital death, overweight patients showed different responses to medications compared with normal weight patients. Intravenous interferon-α, intravenous glucocorticoids, and antifungal drugs were associated with reduced mortality in overweight patients. Intravenous immunoglobulin, oseltamivir, and ribavirin were associated with reduced mortality in normal weight patients.Overweight is a worldwide health problem. We found overweight to be related to the COVID-19 severity but not to in-hospital death. Clinicians should be aware that overweight COVID-19 patients require increased attention for different clinical features and treatment response.