Malaria is an important public health problem worldwide, representing also an obstacle for the development of the countries, mainly in the African continent. Since no effective vaccine has been developed yet, early diagnosis and prompt treatment are the main strategy to control malaria transmission. Many of the drugs used for malaria treatment have the ability to induce apoptosis in different cell types. In addition, apoptosis has also been identified in enucleated cells. The present work is aimed, therefore, to evaluate the pro-apoptotic aptness of chloroquine, quinine, artemisinin and mefloquine on mature erythrocytes by flow cytometry through the detection of cell shrinkage and phosphatidylserine exposure at the cell surface-hallmarks of apoptosis. Although we observed that known apoptosis inducer, such as ionomycin, had led to erythrocyte apoptosis, we were not able to detect any pro-apoptotic effect of the studied antimalarial drugs on these cells. We conclude that chloroquine, quinine, artemisinin and mefloquine may not be able to induce apoptosis in erythrocytes and, therefore, do not seem to contribute to malaria associated erythrocyte destruction and anemia.