Abstract Disclosure: E. Burguera-Couce: None. V.O. Cheng: None. J.G. Monteiro: None. G. Gopalakrishnan: None. Background: Stress hyperglycemia (SH), the physiologic increase in blood glucose during severe illness, has been linked with poor outcomes in certain disease states1. Hyperglycemia in the setting of diabetes (DM) has been well established as a predictor of poor outcomes in Coronavirus disease 2019 (COVID-19) infection2-4. The impact of SH on health outcomes for individuals without DM (NoDM) hospitalized with COVID-19 infection is less clear with studies reporting variable outcomes in this population4-6. Objective: To evaluate the impact of SH on health outcomes among hospitalized individuals with COVID-19Methods: Data from 1001 individuals with SH (defined as ≥ 2 instances of BG above 180 mg/dL) admitted in Rhode Island with COVID-19 infection during the first-wave (March 1-June 30, 2020) and second-wave (July 1, 2020-February 28, 2021) was analyzed. Multivariate logistic regression was conducted to compare DM status for length of stay (LOS), ICU admission, mechanical ventilation (MV) and in-hospital mortality, and was adjusted for age, race/ethnicity, gender, insurance, and wave. Model investigating risk factors associated with poor outcomes (ICU admission, MV or in-hospital mortality) in hospitalized individuals with SH was additionally adjusted to include BMI, Chronic kidney disease (CKD), hypertension (HTN), pulmonary disease, and cardiovascular diseases. Results: 17.0% (170) of the cohort had NoDM. Average age (67.6±13.9), gender (57.1% male) and race/ethnicity (Caucasian/White 48.9%, Hispanic 28.0%, Black 13.2% and Other 10.0%) noted in the overall cohort. Individuals with NoDM were more likely to be Caucasian/White (57.7 vs 47.1%, p-value=0.0122), and more likely to require LOS ≥1-week (OR 2.32[1.57-3.44]), ICU admission (2.26[1.60-3.20]) and MV (3.39[2.35-4.89]). NoDM was also associated with higher in-hospital mortality (3.44[2.39-4.96]). The risk of poor outcomes was significantly higher in NoDM compared to DM (ICU admission 47.7 vs 28.6%, MV 45.3 vs 20.1%, Mortality 41.8 vs. 18.2%). In multivariate analysis, Caucasians/Whites (0.50[0.29-0.87]) were less likely to have poor outcomes than the other races. NoDM (3.55[2.40-5.25]), male gender (1.57[1.16-2.13]), CKD stage 5 (1.94[1.40-2.68]), and admission during the first-wave (2.64[1.89-3.70]) were identified as independent risk factors for poor outcomes in SH associated with COVID-19. Conclusion: Our study showed that individuals without a known diagnosis of diabetes hospitalized with COVID-19 who experienced SH during their hospital course had worse outcomes when compared to individuals with diabetes and hyperglycemia. NoDM, male gender, nonwhite race/ethnicity, CKD stage 5 and admission during the first wave were identified as independent risk factors for poor outcomes in COVID-19 hospitalizations with hyperglycemia. Presentation: 6/1/2024