Background The aim of this study was to investigate the association between serum albumin levels in the ED and the severity of SARS-CoV-2 infection. Methods This is a retrospective observational study conducted from 15 March 2020 to 5 April 2020 at the EDs of three different hospitals in Italy. Data from 296 patients suffering from COVID-19 consecutively evaluated at EDs at which serum albumin levels were routinely measured on patients’ arrival in the ED were analysed. Albumin levels were measured, and whether these levels were associated with the presence of severe SARS-CoV-2 infection or 30-day survival was determined. Generalised estimating equation models were used to assess the relationship between albumin and study outcomes, and restricted cubic spline (RCS) regression was used to plot the adjusted dose-effect relationship for possible clinical confounding factors. Results The mean albumin level recorded on entry was lower in patients with severe SARS-CoV-2 infection than in those whose infections were not severe (3.5 g/dL (SD 0.3) vs 4 g/dL (SD 0.5)) and in patients who had died at 30 days post-ED arrival compared with those who were alive at this time point (3.3 g/dL (SD 0.3) vs 3.8 g/dL (SD 0.4)). Albumin <3.5 g/dL was an independent risk factor for both severe infection and death at 30 days, with adjusted odd ratios of 2.924 (1.509–5.664) and 2.615 (1.131–6.051), respectively. RCS analysis indicated that there was an adjusted dose–response association between the albumin values recorded on ED and the risk of severe infection and death. Conclusion Albumin levels measured on presentation to the ED may identify patients with SARS-CoV-2 infection in whom inflammatory processes are occurring and serve as a potentially useful marker of disease severity and prognosis.