Background: Children with sickle cell anemia (SCA) are at an increased risk of cardiovascular complications. The aim of this study was to assess the role of speckle tracking echocardiography in detecting subclinical myocardial damage in children with SCA. Methods: A cross-sectional case–control study was conducted at the echocardiography laboratory of the military hospital of Tunis between July and December 2018. Thirty patients with SCA were included. A control(C) group including 30 normally developing children was selected and matched to the SCA group by sex and age. We compared between the two groups: conventional echocardiographic parameters including cardiac output, left ventricular ejection fraction (LVEF), thickness and the global longitudinal strain (GLS). The echocardiographic measurements were indexed according to body surface area. The left ventricular (LV) GLS association with clinical characteristics and echocardiographic parameters were also evaluated. Results: Patients and controls were matched for age and sex: the mean age was (11± 2years) in SCA group versus (12± 1 years) in C group with a sex ratio of (1.31 versus 1.27, respectively). Body surface area was comparable. LV hypertrophy and dilation were revealed in the SCA group, whereas measurements were normal in the C group. No significant differences were observed for cardiac output (p=0.4). LVEF were preserved in both groups. However, two-dimensional (2D) LVGLS was impaired in 46% of SCA group (n=14) with mean value of (-21%±3.07 vs -25%±2.98; p<0.01).In SCA group, impaired LVGLS was significantly associated with LV mass (r = – 0.399, p<0.01), LV tele diastolic diameter(r= -0.419, p<0.01) and left atrial volume (r= - 0.399, p< 0.04). In multivariate analysis, LV mass was the only independent factor. Conclusions: In the present study, LVGLS measurement revealed subclinical LV systolic impairment in patients with SCA. Therefore, 2D strain could be beneficial to detect the natural history of LV dysfunction in SCA.