The length of stay (LOS) plays a pivotal role in determining the remuneration of the overcrowding of emergency rooms through the output mechanism due to the unavailability of hospital beds. The advent of COVID-19 pandemic in Italy marked a reorganization of health services with the aim of improving the quality of the services offered. The objective of this study is to evaluate the impact of the COVID-19 pandemic on the LOS of patients through the application of the Define, Measure, Analyze, Improve and Control (DMAIC) cycle methodology of Lean Six Sigma (LSS). The analysis was conducted in the Cardiology department of the Cardarelli Hospital in Naples. Data from the pre-COVID period (2019) and the pandemic period (2020) were statistically evaluated. The results demonstrate that the reduction in patient numbers in 2020 is accompanied by an average increase in LOS compared to 2019. The observed increase in LOS was found to be independent of age, affecting only male patients. Furthermore, the findings revealed that, for both years, male and female patients with comorbidities exhibited a higher LOS on average than their counterparts without comorbidities. The implications of this study are twofold: firstly, the utilization of a LSS to examine the effects of the pandemic will yield significant results that will provide support to doctors in managing their departments, and secondly, it will optimize hospital flows. It is important to acknowledge the limitations of this study, namely the narrow time range and the relatively small sample size.