The COVID-19 pandemic has highlighted a correlation between cardiac complications and elevated cardiac biomarkers, which are linked to poorer clinical outcomes. This study aims to determine the clinical impact of cardiac biomarkers in COVID-19 patients in Latin America. The CARDIO COVID 19-20 Registry is a multicenter observational study across 44 hospitals in Latin America and the Caribbean. It included hospitalized COVID-19 patients (n = 476) who underwent troponin, natriuretic peptide, and D-dimer tests. Patients were grouped based on the number of positive biomarkers. Among the 476 patients tested, 139 had one positive biomarker (Group C), 190 had two (Group B), 118 had three (Group A), and 29 had none (Group D). A directly proportional relationship was observed between the number of positive biomarkers and the incidence of decompensated heart failure. Similarly, there was a proportional relationship between the number of positive biomarkers and increased mortality. In Group B, patients with elevated troponin and natriuretic peptide and those with elevated troponin and D-dimer had 1.4 and 1.5 times higher mortality, respectively, than those with elevated natriuretic peptide and D-dimer. In Latin American COVID-19 patients, a higher number of positive cardiac biomarkers is associated with increased cardiovascular complications and mortality. These findings suggest that cardiac biomarkers should be utilized to guide acute-phase treatment strategies.