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Background: Critically ill patients may show significant weight change in their course of disease during ICU stay. However, what weight changes occur and their effects on patient outcome have not yet been reported to our knowledge. Therefore, we evaluated weight change in critically ill patients in the medical ICU and the effect this may have on clinical outcome. Methods: We measured body weight in patients admitted to the medical ICU daily and evaluated their clinical characteristics and outcome. Results: Thirty-eight patients (M:F = 30:8, mean age = 65.7 ± 12.5) were enrolled. Thirteen patients (34.2%) showed weight gain and the mean change was 12.8 ± 4.2%. In contrast, 25 patients (65.8%) showed weight loss and the mean change was 6.3 ± 6.9%. Patients who showed weight change over 5% or 10% were 26 (68.4%), and 12 (31.6%), respectively, and their mortality rates were 61.5% and 75%, respectively, showing no statistical significance (p > 0.05). However, when the degree of weight change was stratified with < 5%, 5−10% and > 10%, it was associated with death (p = 0.002). Factors like ICU stay, day of mechanical ventilation, initial APACHE II and SOFA score, body mass index (BMI) and serum albumin were not associated with more than 5% change of weight. BMI at admission was only associated with > 10% change of weight (p < 0.05). Conclusions: The majority of critically ill patients showed a significant weight change during their ICU stay and these patients may have a tendency to have worse clinical outcome.