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The COVID-19 pandemic has challenged the entire world, and patients with diabetes mellitus (DM) have been particularly affected. We aimed to evaluate predictors of mortality during the first 30 days of hospitalization in critically ill patients with COVID-19 and comorbid DM. This prospective study included 110 critically ill patients admitted with COVID-19 infection. Thirty-two (29%) patients had a previous diagnosis of DM. Clinical variables, laboratory tests, and vascular biomarkers, such as VCAM-1, syndecan-1, ICAM-1, angiopoietin-1, and angiopoeitin-2, were evaluated after intensive care unit (ICU) admission. A comparison was made between patients with and without DM. No difference in mortality was observed between the groups (48.7 vs 46.9%, P=0.861). In the multivariate Cox regression analysis, VCAM-1 levels at ICU admission (HR: 1 [1-1.001], P<0.006) were associated with death in patients with DM. Among patients with DM, advanced age (HR 1.063 [1.031-1.096], P<0.001), increased Ang-2/Ang-1 ratio (HR: 4.515 [1.803-11.308] P=0.001), and need for dialysis (HR: 3.489 [1.409-8.642], P=0.007) were independent predictors of death. Higher levels of VCAM-1 in patients with DM was better at predicting death of patients with severe COVID-19 and comorbid DM, and their cut-off values were useful for stratifying patients with a worse prognosis. Vascular biomarkers VCAM-1 and Ang-2/Ang-1 ratio were predictors of death in patients with severe COVID-19 and comorbid DM and those without DM. Additionally, kidney injury was associated with an increased risk of death. COVID19 COVID 19 COVID-1 world (DM affected 3 11 infection Thirtytwo Thirty two 29% 29 (29% variables tests VCAM1, VCAM1 VCAM 1, syndecan1, syndecan1 syndecan syndecan-1 ICAM1, ICAM1 ICAM ICAM-1 angiopoietin1, angiopoietin1 angiopoietin angiopoietin-1 angiopoeitin2, angiopoeitin2 angiopoeitin 2, 2 angiopoeitin-2 (ICU 48.7 487 48 7 (48. 469 46 9 46.9% P=0.861. P0861 P P=0.861 . 0 861 P=0.861) analysis VCAM- HR 11.001, 11001 1.001 , 001 [1-1.001] P<0.006 P0006 006 1063 063 1.06 1.0311.096, 10311096 1.031 1.096 031 096 [1.031-1.096] P<0.001, P0001 P<0.001 P<0.001) Ang2/Ang1 Ang2Ang1 AngAng Ang 2/Ang Ang-2/Ang- 4515 4 515 4.51 1.80311.308 180311308 1.803 11.308 803 308 [1.803-11.308 P=0.001, P=0.001 P=0.001) 3489 489 3.48 1.4098.642, 14098642 1.409 8.642 409 8 642 [1.409-8.642] P=0.007 P0007 007 cutoff cut off prognosis Additionally COVID1 COVID- (29 syndecan- ICAM- angiopoietin- angiopoeitin- 48. (48 46.9 P086 P=0.86 86 11.001 1100 1001 1.00 00 [1-1.001 P<0.00 P000 106 06 1.0 0311 1.0311.096 1031109 1031 1.03 1096 1.09 03 09 [1.031-1.096 Ang2 Ang1 Ang2/Ang Ang2Ang 2Ang Ang-2/Ang 451 51 4.5 80311 1.80311.30 18031130 1803 1.80 11308 11.30 80 [1.803-11.30 P=0.00 348 3.4 4098 1.4098.642 1409864 1409 1.40 8642 8.64 40 64 [1.409-8.642 (2 (4 46. P08 P=0.8 11.00 100 [1-1.00 P<0.0 P00 10 1. 1.0311.09 103110 103 109 [1.031-1.09 45 5 4. 8031 1.80311.3 1803113 180 1.8 1130 11.3 [1.803-11.3 P=0.0 34 3. 1.4098.64 140986 140 1.4 864 8.6 6 [1.409-8.64 ( P0 P=0. 11.0 [1-1.0 P<0. 1.0311.0 10311 [1.031-1.0 1.80311. 180311 18 113 11. [1.803-11. 1.4098.6 14098 14 8. [1.409-8.6 P=0 [1-1. P<0 1.0311. [1.031-1. 1.80311 18031 [1.803-11 1.4098. [1.409-8. P= [1-1 P< 1.0311 [1.031-1 1.8031 [1.803-1 1.4098 [1.409-8 [1- [1.031- [1.803- [1.409- [1 [1.031 [1.803 [1.409 [ [1.03 [1.80 [1.40 [1.0 [1.8 [1.4 [1.