Abstract Background COVID-19 infection is characterized by its heterogeneity in clinical presentation. Hospital admission, intensive care unit (ICU) admission and mortality rates have shown wide variations throughout the months. Colombia experienced a high rate of COVID-19 infection, leading to significant morbidity and mortality. To date, there are only a few studies reporting peak variations. Therefore, we aimed to explore the potential reasons for epidemiological changes in COVID-19 with time. Methods This study was conducted at a tertiary referral center in Cartagena, Colombia, between March 7, 2020, and February 28, 2021. We included patients aged > 18 years with suspected or confirmed COVID-19. A diagnosis was made using the reverse-transcriptase polymerase chain reaction (RT-PCR) test. We extracted information from the Colombian National Surveillance System (SIVIGILA). We collected demographic data, such as age, sex, RT-PCR test results, and information on close contacts (awareness of the disease). We categorized the study period into two according to the two peaks defined in Colombia: the first period included weeks 10–35 (March 7–August 30, 2020), and the second period included weeks 36–60 (September 1, 2020-February 28, 2021). We adjusted the weekly overall mortality by covariates to identify potential changes during the pandemic. Results In total, 2761 COVID-19 patients were hospitalized at our institution. The most significant number of cases occurred in the first and second periods during week 21 (peak 1 : 121 patients) and week 50 (peak 2 : 128 patients), respectively.