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The purpose of this study was to investigate cytological markers of cellular senescence-including senescence-associated β-galactosidase (SA-β-gal), senescence-associated heterochromatin foci (SAHF), and parameters of the cytokinesis-block micronucleus (CBMN) cytome assay-in peripheral blood samples from patients who had experienced an acute coronary syndrome accompanied by COVID-19 (Group 2), compared with similar patients without COVID-19 (Group 1). The relative proportion of SA-β-gal-positive leukocytes was approximately threefold higher in patients with a history of COVID-19 compared with Group 1. Group 2 also demonstrated a significantly higher frequency of SAHF-positive leukocytes. According to the CBMN assay, Group 2 showed a significantly higher relative content of binucleated leukocytes with micronuclei, as well as a higher frequency of apoptotic mononuclear cells. No significant differences were observed between the groups in the relative content of binucleated cells with nuclear buds or nucleoplasmic bridges, nor in the proportion of necrotic mononuclear cells. The cytokinesis-block proliferation index was comparable between the groups. The findings of this retrospective study may indicate a detrimental long-term effect of COVID-19 on the manifestation of cellular senescence at the organismal level, and the evaluated markers may be informative for developing new prognostic strategies for this patient population.