Background: Glucose transporter (GLUT) 4 is an insulin-sensitive transporter that uptakes blood glucose into muscles and adipose tissue. This study aimed to investigate serum GLUT4 levels in critically ill children and to examine the potential relationship between serum GLUT4 levels and illness severity.Methods: This was a retrospective study of 77 critically ill children and 33 non-diabetic healthy children (controls; routine health check-up) who were admitted between 07/2015 and 05/2016. Serum GLUT4 was measured using western blotting and enzyme-linked immunosorbent assays. Insulin resistance indexes, clinical data, laboratory parameters, and inflammatory cytokines were assessed.Results: GLUT4 serum levels were higher in critically ill children than in healthy children (90.5 vs. 30.3 µg/L, P<0.001), and in septic shock compared with sepsis (116.8 vs. 64.3 µg/L, P<0.05), but not compared to non-sepsis/systemic inflammatory response syndrome (105.7 µg/L, P>0.05). Compared to healthy children, hyperglycemic patients (n=48) had elevated GLUT4 serum levels (30.3 vs. 103.7 g/L, P<0.001). Serum GLUT4 levels were higher in patients who died (n=16, P<0.05) than in those who survived (n=57). Serum GLUT4 levels were positively correlated with the neutrophil count, creatine kinase levels, and glucose levels (P<0.05). GLUT4 levels for the diagnosis of sepsis had an area under the curve of 0.70 (P=0.03) when using a 51-µg/L cut-off value, resulting in 74.6% sensitivity and 80% specificity.Conclusions: GLUT4 serum levels might be significantly increased in critically ill children compared with healthy children, particularly those in septic shock. Serum GLUT4 could predict disease severity in critically ill children.