BackgroundThe glycemic response to critical COVID‐19 remains uncertain. We aimed to assess the association between COVID‐19, insulin requirements, glycemic control, and mortality in intensive care unit (ICU) patients.MethodsWe conducted a retrospective observational study of 350 COVID‐19 patients and 1067 non‐COVID‐19 patients admitted to the ICU. Insulin requirement was defined as the total units of exogenous insulin required to cover one gram of administered carbohydrates (insulin‐to‐carbohydrate ratio, ICR). We used multivariable generalized linear mixed‐model (GLMM) analysis to assess the association of the interaction between COVID‐19 and ICU‐day with daily ICR, adjusted for fixed and time‐dependent covariates. Glycemic control was assessed after stratification on diabetes and COVID‐19. We used multivariable logistic regression analysis to assess the association between ICR and 90‐day mortality.ResultsThe mean (95% CI) of the mean daily ICR among patients without diabetes was 0.09 (0.08–0.11) U/g and 0.15 (0.11–0.18) U/g in the non‐COVID‐19 group and COVID‐19 group (p = .01), respectively. In diabetes patients, the corresponding ICRs were 0.52 (0.43–0.62) U/g and 0.59 (0.50–0.68) U/g (p = .32). In multivariable GLMM analysis, the interaction between COVID‐19 and ICU‐day was independently associated with ICR (risk estimate 1.22, 95% CI 1.15–1.31, p < .001). COVID‐19 was associated with higher hypoglycemia prevalence irrespective of diabetes status, higher average glucose levels, more pronounced glucose variability, and a lower proportion of glucose values within target range among patients without diabetes. On multivariable logistic regression analysis, the adjusted odds ratio for 90‐day mortality was 1.77 (95% CI 0.94–3.34, p = .076) per one unit increase in mean ICR.ConclusionIn our cohort of ICU patients, COVID‐19 was associated with higher daily insulin requirements per gram of administered carbohydrates, and worse glycemic control. We found no robust association between ICR and increased odds of death at 90 days.