Introduction: Sex differences in the metabolic response to critical illness are unknown. This retrospective analysis examines potential differences in the evolution of insulin sensitivity (SI) and its variability (%ΔSI) between sexes. Significant differences would suggest differences in the metabolic stress response and glycemic response to insulin therapy, and, thus, the need for more personalized glycemic control (GC). Methods: Retrospective data from 145 ICU patients (N=8710 hours) are used to hourly identify hourly model-based SI and its rate of change %ΔSI in 6-hour blocks from ICU admission to 72 hours. The evolution of SI and %ΔSI are compared for males and females. Hypothesis testing (95% confidence interval (CI) bootstrapped difference in medians) assesses if differences are significant, and equivalence testing assesses if differences are clinically equivalent. Results: Females have significantly lower SI levels than males (p<0.05), and this difference is not clinically equivalent (Figure 1; top). Differences in %ΔSI are not significant (p>0.05), and these differences are clinically equivalent (Figure 1; bottom).