Vitamin D deficiency has been associated to respiratory tract infections. We aimed to investigate vitamin D plasma levels in patients with chest infection with and without COVID-19 in a hospitalized population during the second pandemic wave. A prospective study was conducted in a Mediterranean tertiary center referring to 80 patients suffering from chest infection, who were divided into two groups according to a positive test for SARS-CoV-2 infection. The hospitalized COVID-19 patients had a high prevalence of vitamin D deficiency, and these patients also exhibited higher levels of plasma inflammatory markers. Intensive research is required to identify the role and mechanisms of vitamin D in patients with SARSCoV-2 infection and its possible role as a prognostic factor of the disease.