Background: In the context of sickle cell anemia, peripheral blood indexes provide key information that is also potentially influenced by age. Therefore, it is necessary to understand the extent and nature of interactions between sickle cell anemia and age, especially in situations where there is a high prevalence of sickle cell anemia. Methods: In a cross-sectional study of 374 subjects with varying hemoglobin S (HbS) status, we characterized the interaction between age and sickle hemoglobin using principal components analysis. Results: Factor analysis in subjects with hemoglobin AA identified three orthogonal factors - normal erythropoiesis, presence of thalassemia and the aggregability potential of the blood. These three factors were differentially associated with hemoglobin status. Age influenced the association of factors #2 and #3 with hemoglobin status. Conclusion: Our findings suggest that the interaction between age and hemoglobin status needs to be considered in both clinical and public health settings.