Background: Zinc is a trace element with potent immunoregulatory and antiviral properties, and is utilized in the treatment of coronavirus disease 2019 (COVID-19). However, we do not know the clinical significance of serum Zinc levels in COVID-19 patients. The aim of this study was to determine the clinical significance of serum zinc in COVID-19 patients and to establish a correlation with disease severity. Methods: This was a prospective study of fasting zinc levels in COVID-19 patients at the time of hospitalization. An initial comparative analysis was conducted between COVID-19 patients and healthy controls. COVID-19 patients with zinc deficiency were compared to those with normal zinc levels. Results: COVID-19 patients (n = 47) showed significantly lower zinc levels when compared to healthy controls (n = 45): median 74.5 (interquartile range 53.4-94.6) mg/dl vs 105.8 (interquartile range 95.65-120.90) mg/dl (p < 0.001). Amongst the COVID-19 patients, 27 (57.4%) were found to be zinc deficient. These patients were found to have higher rates of complications (p = 0.009), acute respiratory distress syndrome (18.5% vs 0%, p = 0.06), corticosteroid therapy (p = 0.02), prolonged hospital stay (p = 0.05), and increased mortality (18.5% vs 0%, p = 0.06). The odds ratio (OR) of developing complications was 5.54 for zinc deficient COVID-19 patients. Conclusions: The study data clearly show that a significant number of COVID-19 patients were zinc deficient. These zinc deficient patients developed more complications, and the deficiency was associated with a prolonged hospital stay and increased mortality.