Early in 2020, Italy was among the first nations in Europe to be severely impacted by the COVID-19 epidemic. In this study, we want to evaluate, through the application of the Define, Measure, Analyze, Improve, and Control (DMAIC) cycle methodology of Lean Six Sigma (LSS), the impact of Covid-19 on the LOS of patients in the Emergency Department (ED-LOS) of the “Maresca” Hospital based in Torre del Greco Naples (Italy). Statistical analysis was conducted in the study therefore involved a statistical comparison of data between 2019 (pre-covid) and 2020 (during the pandemic). The work was conducted by analyzing the five main phases of the DMAIC cycle. The findings indicated that in 2020, there was an overall increase in emergency department length of stay (ED LOS). However, an exception was observed for patients with yellow and red triage codes, whose ED LOS significantly decreased during the pandemic. The implications of the study were the use of an LSS approach to examine the effects of COVID-19 to achieve significant results that will provide support to doctors for department management, optimizing hospital flows. The limits of the study are the time range and the sample of the reduced data.