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Previous studies associate the disturbance of the Zinc (Zn) status with the severity of the disease and the inflammatory process in the critically ill patient. This decrease in Zn concentrations is an indicator of poor prognosis. Our aim was to evaluate Zn levels at admission and after four days, and to study if lower Zn levels at those days were related to a worse clinical outcome. Observational cohort study at a tertiary Hospital. Recruitment period: 09/04/2020–04/24/2021. Clinical information on hypertension, diabetes mellitus (DM), chronic obstructive pulmonary disease (COPD), or bronchial asthma was collected. Obesity was defined as BMI ≥ 30 Kg/m2. Blood extraction was performed at admission and after 4 days. Zn was measured by atomic absorption using a flame method. Worse clinical outcome was defined as death during admission, intensive critical care unit admission or receiving supplemental oxygen through noninvasive or invasive ventilator care. 129 subjects were invited to participate but only 100 subjects completed the survey. According to ROC curve [AUC= 0.63 (95% CI 0.60–0.66)], Zn < 79 μg/dL showed the best performance to detect a worse outcome (Sn=0.85; Sp=0.36). Patients with Zn < 79 μg/dL were older (70 vs 61 y; p = 0.002) with no differences by sex. Most patients presented with fever, dysthermic symptoms and cough, without differences between groups. Pre-existing comorbid conditions did not differ significantly between groups. Less obese subjects were found in the Zn < 79 μg/dL group (21.4 vs 43.3%, p = 0.025). In the univariate analysis, Zn < 79 μg/dL at hospital admission was related to a worse outcome (p = 0.044), but after adjusting for age, C-reactive protein, and obesity there was no difference, but a tendency towards a worse prognosis [OR 2.20 (0.63–7.70), p = 0.215]. Zn levels increased in both groups after 4 days (66.6 vs 73.1 μg/dL at admission, and 72.2 vs 80.5 μg/dL at 4th day), with ns. difference (p = 0.214). Zn < 79 μg/dL at admission for a moderate to severe COVID-19 infection could be related to a worse outcome, although after adjustment for age, C-reactive protein levels and obesity, this Zn level threshold did not show statistically significant difference in the composite end point, but a tendency towards a worse prognosis. In addition, patients with the best clinical evolution showed higher serum Zn levels at 4th day after hospital admission than the patients with a worse prognosis. [ABSTRACT FROM AUTHOR]