Background Pericardial diseases manifest in various clinical forms, including acute pericarditis, constrictive pericarditis, pericardial effusion, and cardiac tamponade, with acute pericarditis being the most prevalent. These conditions significantly contribute to mortality rates. Therefore, this article aimed to analyze mortality trends in the Brazilian population based on age and sex, shedding light on the impact of pericardial diseases on public health outcomes. Methods This is a retrospective time-series analysis of pericardial disease mortality rates in Brazil (2000-2022). Data was obtained from the Department of Informatics of the Unified Health System (DATASUS), and the 10th edition of the International Classification of Diseases (ICD-10) codes: I30, I31, and I32 were included for analysis. We gathered population and demographic data categorized by age range and sex from the Brazilian Institute of Geography and Statistics (IBGE). Subsequently, we computed the age-standardized mortality rate per 100,000 individuals and assessed the annual percentage changes (APCs) and average annual percentage changes (AAPCs) using joinpoint regression, along with their corresponding 95% confidence intervals (CIs). Results In terms of mortality trends based on sex, overall mortality rates remained stable for males and combined sexes over the study period. However, there was a notable increase in mortality rates among females (AAPC=1.18), particularly between 2020 and 2022, with a significant APC of 27.55. Analyzing pericardial diseases across different age groups (20 to 80 years and above), it wasobserved that mortality rates significantly increased in the 70-79 and 80 years and above age groups throughout the study period (AAPC=1.0339 and AAPC=3.4587, respectively). These two age groups experienced the highest significant rise in mortality between 2020 and 2022. Other age groups did not exhibit a significant change in AAPC. Conclusions This comprehensive analysis spanning two decades (2000-2022), examined the mortality trends of pericardial diseases in Brazil and revealed relative stability overall. Males exhibited an overall higher mortality number due to pericardial diseases; however, females showed the most significant increase in mortality trend throughout the whole period. In the first segment (2000-2015), mortality rose across all cohorts, which was attributed to substandard healthcare facilities and infectious diseases like tuberculosis. The second segment (2016-2020) saw a decline in mortality, likely due to improved healthcare, particularly the increased availability of echocardiograms. However, the third segment (2020-2022) witnessed a sharp rise in mortality, coinciding with the COVID-19 pandemic, with post-COVID-19 symptoms, particularly pericarditis. Pericarditis-related death rates declined compared to pericardial effusion, and mortality rates correlated directly with age, with older cohorts experiencing higher mortality due to increased comorbidities, and decline in health and immunocompetency.