PURPOSE: To determine predictors of in-hospital mortality related to COVID-19 in oldest-old patients. DESIGN: Single-center observational study. SETTING AND PARTICIPANTS: Patients >/= 75 years admitted to an Acute Geriatric Unit with COVID-19. METHODS: Data from hospital admission were retrieved from the electronic medical records: demographics, geriatric syndromes (delirium, falls, polypharmacy, functional and cognitive status) co-morbidities, previous treatments, clinical, laboratory, and radiographic characteristics. Cox proportional hazard models were used to evaluate in-hospital mortality. RESULTS: Three hundred patients were consecutively included (62.7% females, mean age of 86.3 +/- 6.6 years). Barthel Index (BI) was < 60 in 127 patients (42.8%) and 126 (42.0%) had Charlson Index CI >/= 3. Most patients (216; 72.7%) were frail (Clinical Frailty Scale >/= 5) and 134 patients (45.1%) had dementia of some degree. The overall in-hospital mortality rate was 37%. The following factors were associated with higher in-hospital mortality in a multi-variant analysis: CURB-65 score = 3-5 (HR 7.99, 95% CI 3.55-19.96, p < 0.001), incident delirium (HR 1.72, 1.10-2.70, p = 0.017) and dementia (HR 3.01, 95% CI 1.37-6.705, p = 0.017). Protective factors were concurrent use of angiotensin-converting enzyme inhibitors (HR 0.42, 95% CI 0.25-0.72, p = 0.002) or prescription of hydroxychloroquine (HC 0.37 95% CI 0.22-0.62, p < 0.001) treatment during admission. CONCLUSIONS AND IMPLICATIONS: Our findings suggest that recognition of geriatric syndromes together with the CURB-65 score may be useful tools to help clinicians establish the prognosis of oldest-old patients admitted to hospital with COVID-19.