© 2021 American Society for Parenteral and Enteral NutritionBackground: Ghrelin is a hormone that regulates appetite and energy metabolism. The change of serial serum total and acylated ghrelin levels during hospital stays of critical patients are unknown. In addition, the relationship of this change with the clinical results of patients in the intensive care unit (ICU) is also unknown. The aim of this study was to determine serum total and acylated ghrelin levels serially in critically ill patients. Methods: This prospective study was performed in the ICU. Patients who were >18 years old and stayed in ICU for >48 h were included in the study. Serum total and acylated ghrelin concentrations were measured at baseline in all participants and serially on the 2nd, 5th, and 10th day after entry into the study in those who remained in the ICU. Results: A total of 60 participants were included. The mean age was 56 ± 21 years. (Baseline, 2nd, 5th, and 10th day median serum total ghrelin levels were 3551 (1651–3995), 3485.20 (1379–4071), 3359 (1167–3919), and 3355 pg/ml (2207–3843), respectively. Baseline, 2nd, 5th, and 10th day acylated ghrelin levels were 47 (0–673), 50 (0–730), 73 (0–808), and 125 pg/ml (0–689), respectively. There was no significant difference between total ghrelin/acylated ghrelin levels and mortality (P >.05). ICU mortality was 30%. Conclusion: Ghrelin levels were decreased slightly and acylated ghrelin levels increased substantially over time in critically ill patients. There were no differences between serum total ghrelin/acylated ghrelin levels and ICU mortality.