Acute myocardial infarction (AMI), with a very relevant global disease burden, remains the major mortality and morbidity cause among all cardiovascular diseases. Patient prognosis is strictly dependent on early diagnosis and the adoption of adequate interventions. AMI diagnosis requires constant optimization, particularly considering the individuals at higher risk (or more vulnerable to worse outcomes) such as patients with diabetes mellitus and atherosclerosis. Herein, we investigated the levels of peripheral blood EPCs and immune cell-subsets from myeloid and lymphoid lineages, as well as their temporal dynamics, in the quest for new prognostic biomarkers of AMI. We collected blood from 18 hospitalized patients (days 3 and 7 after AMI onset) and 16 healthy volunteers, and resolved their circulating PBMC populations via flow cytometry. Overall, our data demonstrate a significant decrease in peripheral EPCs and CD8+ T cells, three days following an AMI. EPCs appear to be functionally impaired in AMI patients, and their circulating numbers associate with cardiac vessel lesions. Furthermore, CD8+ T cells (and even M1-macrophages) in the periphery, in combination with the classical laboratory determinations, may serve as high accuracy biomarkers of AMI, potentially aiding to prevent worse AMI outcomes.