Pulmonary atelectasis presumably promotes and facilitates lung injury. However, data are limited on its direct and remote relation to inflammation. We aimed to assess regional 2-deoxy-2-[18F]-fluoro-D-glucose (18F-FDG) kinetics representative of inflammation in atelectatic and normally aerated regions in models of early lung injury. We studied supine sheep in four groups: Permissive Atelectasis (n=6)-16 hours protective tidal volume (VT) and zero positive end-expiratory pressure; Mild (n=5) and Moderate Endotoxemia (n=6)- 20-24 hours protective ventilation and intravenous lipopolysaccharide (Mild=2.5 and Moderate=10.0 ng/kg/min), and Surfactant Depletion (n=6)-saline lung lavage and 4 hours high VT. Measurements performed immediately after anesthesia induction served as controls (n=8). Atelectasis was defined as regions of gas fraction <0.1 in transmission or computed tomography scans. 18F-FDG kinetics measured with positron emission tomography were analyzed with a three-compartment model. 18F-FDG net uptake rate in atelectatic tissue was larger during Moderate Endotoxemia (0.0092 0.0019/min) than controls (0.0051 0.0014/min, p = 0.01). 18F-FDG phosphorylation rate in atelectatic tissue was larger in both endotoxemia groups (0.0287 0.0075/min) than controls (0.0198 0.0039/min, p = 0.05) while the 18F-FDG volume of distribution was not significantly different among groups. Additionally, normally aerated regions showed larger 18F-FDG uptake during Permissive Atelectasis (0.0031 0.0005/min, p < 0.01), Mild (0.0028 0.0006/min, p = 0.04), and Moderate Endotoxemia (0.0039 0.0005/min, p < 0.01) than controls (0.0020 0.0003/min). Atelectatic regions present increased metabolic activation during moderate endotoxemia mostly due to increased 18F-FDG phosphorylation, indicative of increased cellular metabolic activation. Increased 18F-FDG uptake in normally aerated regions during permissive atelectasis suggests an injurious remote effect of atelectasis even with protective tidal volumes. Copyright 2020 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.