Introduction: The global spread of the SARS-CoV-2 pandemic led to a serious health, social and economic global crisis. This pandemic was and remains the most important health emergency worldwide, for which all professionals have been called to provide diagnosis and treatment support. Despite early concerns about safety, forensic medicine has contributed to a better understanding of the pathological mechanisms involved. Objective: This study aims to describe and analyze the postmortem pathological findings in confirmed SARS-CoV-2 cases, emphasizing the contribution of forensic autopsies to elucidating the mechanisms of death and associated comorbidities. Methods: A retrospective study was conducted on 279 autopsies between 2020 and 2022. Demographic, clinical, and pathological data were collected and statistically analyzed. Results: Following the descriptive analysis of the cases included in the study, as well as the analysis of the relevant scientific literature, the major impact of the COVID-19 pandemic was highlighted in terms of the death mechanisms involved, occurring consequences and induced changes. Conclusions: Autopsies remain the essential tools for investigating COVID-19-related deaths. The findings confirm that SARS-CoV-2 primarily affects the pulmonary and cardiovascular systems. However, the overlap between “death from” and “death with” COVID-19 highlights the need for standardized postmortem diagnostic criteria and comprehensive clinical–pathological correlation.